3D Structured illumination microscopy (SIM)  enables visualisation of the glomerular filtration barrier, using multiplex  immunofluorescence  staining for markers for podocytes ( synaptopodin ,  nephrin ),  endothelial cells  ( EHD3 ), and the  glomerular basement membrane  ( agrin ).


Confocal microscopy  can reveal changes in the processes of  Müller cells , in the  retina , shown here in the  rat . On the left,  GFAP  expression is predominant in the  inner retinal layers .        localized to the innermost  layers of the retina ; on the right GFAP-positive fibers show a thickening in Müller cell processes indicating  gliosis .


Vasoactive modulators, released from astrocytic endfeet, act on smooth muscle cells in arterioles, and pericytes in capillaries to regulate the  vascular tone .


Glomerular podocytes possess a diverse array of  surface-expressed proteins  that contribute to the selective filtration of solutes across the glomerular barrier, thereby maintaining fluid homeostasis within the body.


This  SEM  image illustrates the communication between osteocytes (Ocy) and transcortical vessels (TCV) via their endfeet (yellow arrows) to facilitate mitochondrial transfer.


Ramified microglia in a rat  cortex  before  traumatic brain injury .


Amoeboid microglia after traumatic brain injury.


Effacement of foot processes (FP) of podocytes is evident in this  scanning electron microscopy  (SEM) image, enhanced with false coloring for improved visualization.


The 154 kb chloroplast DNA map of a model flowering plant ( Arabidopsis thaliana : Brassicaceae) showing genes and inverted repeats.


Chloroplast DNA replication via multiple D loop mechanisms. Adapted from Krishnan NM, Rao BJ's paper "A comparative approach to elucidate chloroplast genome replication."


Over time, base changes in the DNA sequence can arise from deamination mutations. When adenine is deaminated, it becomes hypoxanthine, which can pair with cytosine. During replication, the cytosine will pair with guanine, causing an A → G base change.


A circular chromosome, showing DNA replication proceeding bidirectionally, with two replication forks generated at the "origin". Each half of the chromosome replicated by one replication fork is called a "replichore". (Graphic computer art by Daniel Yuen)


Bidirectional replication in a circular chromosome.


oriC  motifs in bacteria


Most circular bacterial chromosomes are replicated bidirectionally, starting at one point of origin and replicating in two directions away from the origin. This results in semiconservative replication, in which each new identical DNA molecule contains one template strand from the original molecule, shown as the solid lines, and one new strand, shown as the dotted lines.


Forebrain  neuronal culture after 40 days of differentiation from  induced human pluripotent stem cells . iPSCs from a patient with  familial Alzheimer's disease , a mutation in the  PSEN1  gene. TUJ-1-positive cells express a marker (β3-tubulin) of mature neurons (red).  GABA-positive cells  (green). Cell nuclei are stained with DAPI (blue).


Figure 1: Methods of dynamin-dependent and independent clathrin-independent endocytosis.


Figure 2: Clathrin-independent endocytic processes uses (a) FEME, (b) CLIC/GEEC, and (c) CL-Lect hypothesis


Cystolith from leaf of  Ficus elastica


Drawing of a cystolith from leaf of  Ficus elastica


Proteins in different  cellular compartments  and structures  tagged  with  green fluorescent protein


The cytoskeleton consists of (a) microtubules, (b) microfilaments, and (c) intermediate filaments. [ 1 ]


Cross section diagram through the cilium, showing the “9 + 2” arrangement of microtubules


The cytosol is a crowded solution of many different types of molecules that occupy up to 30% of the cytoplasmic volume. [ 1 ]


Intracellular fluid content in humans


Carboxysomes  are protein-enclosed  bacterial microcompartments  within the cytosol. On the left is an  electron microscope  image of carboxysomes, and on the right a model of their structure.


Illustration of the plasmodesmata structure spanning the cell wall (CW). The desmotubule (DM) is shown as a continuation of the endoplasmic reticulum (ER), with various membrane proteins linking it to the plasma membrane (PM).


Figure1. Illustrates the movement of a diplosome in the early stages of mitosis as described in  Diplosome in Mitosis .


The different types of endocytosis


Schematic drawing illustrating clathrin-mediated (left) and clathrin-independent endocytosis (right) of  synaptic vesicle   membranes


From left to right: Phagocytosis, Pinocytosis, Receptor-mediated endocytosis.


Detail of the endomembrane system and its components


Diagram of the nucleus with the nuclear envelope shown as the orange portion


1   Nucleus     2   Nuclear pore     3  Rough endoplasmic reticulum (RER)     4  Smooth endoplasmic reticulum (SER)     5   Ribosome  on the rough ER     6   Proteins  that are transported     7  Transport  vesicle     8   Golgi apparatus     9  Cis face of the Golgi apparatus     10  Trans face of the Golgi apparatus     11  Cisternae of the Golgi apparatus


By using  electron microscope , ribosomes ("particles") on the  rough endoplasmic reticulum  can be observed


Micrograph of Golgi apparatus, visible as a stack of semicircular black rings near the bottom. Numerous circular vesicles can be seen in proximity to the organelle.


Detailed illustration of the plasma membrane. Including the structure of a  phospholipid .


Shown is a micrograph of an amoeba; the darker pink nucleus is central to the eukaryotic cell, with the majority of the rest of the cell's body belonging to the endoplasm. Though not visible, the ectoplasm resides directly internal to the plasma membrane.


This is a perikaryon of a nerve cell, displayed here because of the obvious cytoplasmic granules. The granules, which appear almost black due to their high electron density, take up a large portion of the endoplasm. They are suspended in cytosol - the fluid component of the cytoplasm.


This image displays the 3 main processes of cell respiration - the pathway from which the cell obtains energy in the form of ATP. These processes include glycolysis, the citric acid cycle, and the electron transport chain.


Summary of ESCRT machinery and accessory proteins. [ 3 ] [ 6 ]


Trafficking of membrane bound proteins to the lysosome using ESCRT machinery.  Membrane bound proteins are taken into the cell via endocytosis. Ubiquitin tags on the protein are recognized by ESCRT machinery and recruited to the endosome. Multivesicular bodies are formed, which then fuse with the lysosome where these proteins are degraded. Adapted from. [ 1 ]


Recruitment of ESCRT Complexes to the Midbody.  Cep-55 binds MKLP1. Cep-55 recruits ESCRT-I and ALIX. ESCRT-I and ALIX recruit ESCRT-III. ESCRT-III forms spiral around membrane neck between daughter cells leading to constriction and cleavage. Adapted from. [ 22 ]


Retroviral budding of HIV.  A) Accumulation of viral proteins under the cell membrane causes the virus to protrude outward. B) A constriction is formed by the ESCRT complexes at the base of membrane protrusion causing formation of a virus containing vesicle. C) The bud pinches off leaving a free extracellular virion.  (Photo provided by Dr. Matthew Gonda (Wikimedia Commons: Nov. 1998), National Cancer Institute Image ID: 2382)


Fluid mosaic model of a  cell membrane


The Frye-Edidin experiment showed that when two cells are fused the proteins of both diffuse around the membrane and mingle rather than being locked to their area of the membrane.


S.cerevisiae  septins Septin ring-like structures (in green) can pinch cell membranes and split them into subdomains.


Connexon pairing across membranes bridges the gap between two cells and between vesicles to membranes. [ 20 ]


Light microscope images do not allow us to see connexons or innexons themselves but do let us see the fluorescing dye injected into one cell moving into neighboring cells when gap junctions are known to be present. [ 38 ]


Cell pannexin tree with white squares having communication proteins yet to be discovered


Effects of perinexal width on ephaptic coupling, for G gap = 0 nS


Eye lens showing arrangement of fiber cells with photos of gap junction plaques from different regions


The Golgin  GMAP210  has functional regions at both ends.


The ALPS of GMAP210 binds to curved, but not flat, lipid layers


GRASP domain alignment of  GRASP55  and the GRASP homologue of  Cryptococcus neoformans


Microinjection of antibodies to GRASP65 prevents normal Golgi stack formation.


Beta cell  with insulin granules, which are the dark black spots surrounded by a white area called a halo.


Starch granules in potato cells.


Assembly and disassembly of stress granules.


Cartoon of the dividing epithelium cell surrounded by epithelium tissue. Spindle apparatus rotates inside the cell. The rotation is a result of astral microtubules pulling towards tri-cellular-junctions (TCJ), signaling centers localized at the regions where three cells meet.


In  histopathology , pathologic homogenization is seen as a loss of variations, such as of  collagen  in  lichen sclerosus  (pictured).


Nostoc  with hormogonia


Micrographia cells [ 1 ]  in 1665.   But I couldn't find with my microscope, breath or any other way I have tried, a passage out of one cell into another, yet I cannot conclude, that there aren't any passages that exist that the plant juices must pass through .


Cell signalling


4 types of cell junction simplified


Epithelium TCJ


Cell pannexin tree


Fungal hypha


Plasmodesma allowing the symplast pathway


Tubular bridges for bronchial epithelial cell migration and communication


Complete neuron cell diagram


Nervous systems of sponges (porifera) and placozoans


Ctenophore neural systems.


Paristatoid wasp on caterpillar


Simplified structure of a mitochondrion


Electron transport chain and intermembrane space of a mitochondrion


Apoptotic components released from the intermembrane space of a mitochondrion


Simplified structure of a chloroplast


Simplified structure of a eukaryotic cell nucleus


A microscope picture of a cell's invadopodium.


Red arrows indicate secreted lamellar bodies, and green arrows indicate lamellar bodies in the cytoplasm. Scale bar = 200 nm.


Lysosomes digest material. Step one shows material entering a food vacuole through the plasma membrane, a process known as endocytosis. In step two a lysosome with an active hydrolytic enzyme comes into the pictures as the food vacuole moves away from the plasma membrane. Step three consists of the lysosome fusing with the food vacuole and hydrolytic enzymes entering the food vacuole. In the final step, step four, hydrolytic enzymes digest the food particles. [ 5 ]


TEM views of various vesicular compartments. Lysosomes are denoted by "Ly". They are dyed dark due to their acidity; in the center of the top image, a Golgi Apparatus can be seen, distal from the cell membrane relative to the lysosome .


The lysosome is shown in purple, as an endpoint in endocytotic sorting. AP2 is necessary for vesicle formation, whereas the mannose-6-receptor is necessary for sorting hydrolase into the lysosome's lumen.


A  High resolution 3D live-cell fluorescence image of a tunneling nanotube (TNT) (white arrow) connecting two primary mesothelial cells. Scale bar: 20 μm. B  Depiction of a TNT (black arrow) between two cells with scanning electron microscopy. Scale bar: 10 μm. C  Fluorescently labeled F-actin (white arrow) present in TNTs between individual HPMCs. Scale bar: 20 μm. D  Scanning electron microscope image of a potential TNT precursor (black arrowhead). Insert shows a fluorescence microscopic image of filopodia-like protrusions (white arrowhead) approaching a neighboring cell. Scale bar: 2 μm. [ 1 ]


3D live-cell microscopy of immunofluorescent rat PC12 cells demonstrating tunneling nanotubes. From one of the first published papers to describe the phenomenon in 2004.  [ 7 ]


Microtubule and tubulin metrics [ 1 ]


Microtubules are one of the cytoskeletal filament systems in eukaryotic cells. The microtubule cytoskeleton is involved in the transport of material within cells, carried out by motor proteins that move on the surface of the microtubule.


Cartoon representation of the structure of α(yellow)/β(red)-tubulin heterodimer, GTP and GDP. [ 11 ]


Components of the  eukaryotic  cytoskeleton.  Actin filaments  are shown in red,  microtubules  are in green, and the  nuclei  are in blue. The cytoskeleton provides the cell with an inner framework and enables it to move and change shape.


Image of a fibroblast cell containing fluorescently labeled actin (red) and microtubules (green).


A cytoplasmic dynein motor bound to a microtubule.


A kinesin molecule bound to a microtubule.


A 3D diagram of a centriole. Each circle represents one microtubule. In total there are 27 microtubules organized into 9 bundles of 3.


This diagram depicts the organization of a typical mitotic spindle found in animal cells.  Shown here are the three main types of microtubules during mitosis and how they are oriented in the cell and the mitotic spindle.


Mitochondrial network (green) in two human cells ( HeLa cells )


Mitochondria, mammalian lung - TEM (2)


ATP synthesis as seen from the perspective of the matrix. Conditions produced by the relationships between the catabolic pathways (citric acid cycle and oxidative phosphorylation) and structural makeup (lipid bilayer and electron transport chain) of matrix facilitate ATP synthesis.


Ciliates are unicellular eukaryotes that display nuclear dimorphism involving a macronucleus and a micronucleus.


Tetrahymena  provide an example of a cell that displays nuclear dimorphism. It includes a micronucleus and macronucleus, and it has been very helpful in various research.


The location of NORs and the nucleolar cycle in human cells.


Silver-stained nucleolus organizer region (arrow) at the tip of a chromosome of the Gecko  Lepidodactylus lugubris


The DJ forms a perinucleolar anchor for rDNA repeats.


The  protoplasmic  material of the nucleus including the  nucleolus  labelled as nucleoplasm.


Polish - German   botanist  and namer of nucleoplasm,  Eduard Strasburger .


An example of the  sodium-potassium pump , a  P-type ATPase , which controls the ionic gradient across the  cell membrane  and the  nuclear envelope  as well as the ionic makeup of the nucleoplasm through the selective pumping of  sodium  and  potassium   ions .


Histology of a null cell adenoma


(A) Electron micrograph of  Halothiobacillus neapolitanus  cells, arrows highlight  carboxysomes . (B) Image of intact carboxysomes isolated from  H. neapolitanus . Scale bars are 100 nm. [ 23 ]


Structure of  Candidatus  Brocadia anammoxidans , showing an  anammoxosome  and intracytoplasmic membrane


An overlay of a fluorescence micrograph (green) onto a DIC image of a HeLa cell expressing a Yellow fluorescent Protein fusion of Paraspeckle Protein 1 (PSP1): 1. cytoplasm; 2. nucleus; 3. nucleolus; 4. paraspeckles


West et al. (2016) [ 7 ]  suggest that the NEAT1  is folded and bound to  paraspeckle core proteins to first form units, which are bridged together by FUS proteins to form the ordered paraspeckle sphere. [ 8 ]


Phragmosome formation in a highly vacuolated plant cell. From top to bottom: 1) Interphase cell with large central vacuole. 2) Cytoplasmic strands starting to penetrate vacuole. 3) Nucleus migration into center and formation of the phragmosome. 4) Phragmosome formation completed and formation of preprophase band marking future cell division plane.


The structure of a primary plasmodesma. CW= cell wall , CA= callose , PM= plasma membrane , ER= endoplasmic reticulum , DM=desmotubule, Red circles= actin , Purple circles and spokes=other unidentified proteins [ 1 ]


Tobacco mosaic virus movement protein 30 localizes to plasmodesmata


Sketch of a longitudinal ultrathin section through a typical motile bacterium bearing a flagellum and surrounding polar organelle at one end of the cell.


Elements of the  Caulobacter crescentus  cytoskeleton. The prokaryotic cytoskeletal elements are matched with their eukaryotic homologue and hypothesized cellular function. [ 1 ]


Jessica Polka 's electron micrograph of negatively stained purified type 51 R bodies in their extended (low pH) state


Schematic illustration of the supramolecular architecture of the major classes of prokaryotic cell envelopes containing surface (S) layers. S-layers in archaea with glycoprotein lattices as exclusive wall component are composed either of mushroom-like subunits with pillar-like, hydrophobic trans-membrane domains (a), or lipid-modified glycoprotein subunits (b). Individual S-layers can be composed of glycoproteins possessing both types of membrane anchoring mechanisms. Few archaea possess a rigid wall layer (e.g. pseudomurein in methanogenic organisms) as intermediate layer between the plasma membrane and the S-layer (c). In Gram-positive bacteria (d) the S-layer (glyco)proteins are bound to the rigid peptidoglycan-containing layer via secondary cell wall polymers. In Gram-negative bacteria (e) the S-layer is closely associated with the lipopolysaccharide of the outer membrane. Figure and figure legend were copied from Sleytr  et al.  2014, [ 2 ]  which is available under a  Creative Commons Attribution 3.0 International (CC BY 3.0) licence   .


Plant cell overview, showing secondary cell wall.


Sepate junction in developing trachea in  Drosophila


Micrograph  showing condensed  chromosomes  in  blue ,  kinetochores  in  pink , and  microtubules  in  green  during  metaphase  of  mitosis


This diagram depicts the organization of a typical mitotic spindle found in animal cells. Chromosomes are attached to  kinetochore   microtubules  via a multiprotein complex called the kinetochore. Polar microtubules interdigitate at the spindle midzone and push the spindle poles apart via  motor proteins .  Astral microtubules  anchor the spindle poles to the  cell membrane . Microtubule polymerization is nucleated at the  microtubule organizing center .


In the centrosome-mediated "search and capture" model (left), microtubules nucleated from centrosomes contact chromosomes by chance and become stabilized at kinetochores to form the spindle. In the chromatin-mediated "self-organization" model (right), microtubules are nucleated around the vicinity of mitotic chromatin and organized into a bipolar array by motor proteins.


Cartoon of the dividing epithelium cell surrounded by epithelium tissue. Spindle apparatus rotates inside the cell. The rotation is a result of astral microtubules pulling towards tri-cellular-junctions (TCJ), signaling centers localized at the regions where three cells meet.


Depiction of the transmembrane proteins that make up tight junctions: occludin, claudins, and JAM proteins.


TEM  of rat kidney tissue shows a protein dense tight junction (three dark lines) at ~55,000x magnification.


Occludin interacting with GEF-H1/Lfc, which then activates RHOA, a regulator of cell differentiation and motility.


The ultrastructure of a single  bacterial cell  ( Bacillus subtilis ). The scale bar is 200  nm .


Plant cell structure


Animal cell structure


The  anthocyanin -storing vacuoles of  Rhoeo spathacea , a  spiderwort , in cells that have plasmolyzed


An overview of the trafficking of some adaptor protein (AP) complexes.


Adaptor Protein complexes and COPI-F subcomplex. [ 1 ]


Adaptor Protein, COPI and TSET complexes.


More trafficking pathways. Note, the colors are not the same as in the lead figure


A rendering of a COPII tube.


The early evolution of adaptor protein complexes


The evolution of TSET, COPI and APs from the Last Eukaryotic Common Ancestor


Production of a clathrin coated vesicle


Electron microscope image of a coated vesicle. EM series showing the budding of these kind of vesicles can be seen  [ 8 ]  and  [ 9 ]


A small portion of an accessory protein binds specifically to part of AP-2 complex


Protein phosphorylation allows specific interactions with a clathrin adaptor protein complex


A pair of  micrographs  of a cytopathology specimen showing a 3-dimensional cluster of cancerous cells ( serous carcinoma )


An  adenocarcinoma  with typical features as can be seen on cytopathology


Micrograph  of a pilocytic astrocytoma, showing characteristic bipolar cells with long pilocytic (hair-like) processes. Smear preparation.  H&E stain


A  micrograph  of an exfoliative cytopathology specimen ( Pap test ,  Pap stain )


Brushes used to collect samples for cytology.


Example of a cytocentrifuge


Lymphoma  cells in  cerebrospinal fluid


Micrograph  showing the viral cytopathic effect of  herpes simplex virus  (multi-nucleation, ground glass chromatin).  Pap test .  Pap stain .


Bronchoalveolar lavage  specimen stained with Diff-Quik


A physician's hands are seen performing a needle biopsy to determine the nature of a lump, either a fluid-filled cyst or solid tumor.


FNA of pancreatic tissue. An adenocarcinoma is seen on the left, normal ductal epithelium on the right.


Histopathology of a gemistocytic  astrocytoma . Neoplastic gemistocytes are angular shaped with abundant, glassy, eosinophilic cytoplasm and eccentric nuclei with distinct nucleoli.


A  Pap test  showing a low-grade squamous intraepithelial lesion (LSIL).  Pap stain .


Lipid-laden alveolar macrophages in a case of  vaping-associated pulmonary injury . Left:  Papanicolaou stain ; right:  Oil Red O  stain. [ 1 ]


Microscopic photograph of small cell lung carcinoma under high power.


Retroperitoneal  lymphadenopathies of testicular  seminoma  embrace the  aorta .  Computed tomography  image.


Medical ultrasonography  of a typical normal lymph node: smooth, gently lobulated oval with a hypoechoic cortex measuring less than 3 mm in thickness with a central echogenic hilum. [ 26 ]


Ultrasonography of a suspected malignant lymph node: - Absence of the fatty hilum - Increased focal cortical thickness greater than 3 cm -  Doppler ultrasonography  that shows hyperaemic blood flow in the hilum and central cortex and/or abnormal (non-hilar cortical) blood flow. [ 26 ]


Inflammatory localized lymphadenopathy at right mandibular angle


Micrograph  of  dermatopathic lymphadenopathy , a type of lymphadenopathy.  H&E stain .


Micrograph showing navicular cell in extremely high magnification


Sample collection for thin-prep-cytology from the cervix uteri of a 39-years-old multiparous woman (4 pregnancies). The cervical brush is visible just before entering the cervix uteri.


Transformation zone types, determining the Pap test location: [ 66 ] Type 1: Completely ectocervical. Type 2: Endocervical component but fully visible. Type 3: Endocervical component, not fully visible.


Cervix in relation to upper part of vagina and posterior portion of uterus.


Squamous metaplasia of the cervix, with typical features. Pap stain.


Papanicolaou stain showing a low-grade  squamous intraepithelial lesion  (LSIL) from a  Pap test .  Cell nuclei  stained blue.


Blood film  with  Giemsa stain .  Monocytes  surrounded by  erythrocytes .


Blood film  stained with  Giemsa  showing  Plasmodium  (center of image), the parasite that causes  malaria  infections.


Bronchoalveolar lavage  specimen stained with  Diff-Quik , a commercial Romanowsky stain variant widely used in cytopathology


Dmitri Leonidovich Romanowsky (1861-1921)


Ernst Malachowsky


Gustav Giemsa


Frontal chest  X-ray  showing a probable S2–S3 small cell carcinoma in the right side lung.


Histopathology of small-cell carcinoma, with typical findings. [ 30 ]


Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy.  H&E stain .


Pie chart showing incidence of small-cell lung cancer (shown in red at right), as compared to other  lung cancer  types, with fractions of smokers versus non-smokers shown for each type. [ 80 ]


Cross-sectional view of the structures that can be formed by phospholipids in an aqueous solution


A fluid membrane model of the phospholipid bilayer.


N -Acetylglucosamine molecule


As an action potential (nerve impulse) travels down an  axon  there is a change in electric polarity across the  membrane  of the axon. In response to a signal from another  neuron , sodium- (Na + ) and potassium- (K + )–gated  ion channels  open and close as the membrane reaches its  threshold potential . Na +  channels open at the beginning of the action potential, and Na +  moves into the axon, causing  depolarization .  Repolarization  occurs when K +  channels open and K +  moves out of the axon, creating a change in electric polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the  axon terminal  where it signals other neurons.


Shape of a typical action potential. The membrane potential remains near a baseline level until at some point in time, it abruptly spikes upward and then rapidly falls.


Approximate plot of a typical action potential shows its various phases as the action potential passes a point on a  cell membrane . The membrane potential starts out at approximately −70 mV at time zero. A stimulus is applied at time = 1 ms, which raises the membrane potential above −55 mV (the threshold potential). After the stimulus is applied, the membrane potential rapidly rises to a peak potential of +40 mV at time = 2 ms. Just as quickly, the potential then drops and overshoots to −90 mV at time = 3 ms, and finally the resting potential of −70 mV is reestablished at time = 5 ms.


Action potential propagation along an axon


Ion movement during an action potential. Key:  a) Sodium (Na + ) ion. b) Potassium (K + ) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump.  In the stages of an action potential, the permeability of the membrane of the neuron changes. At the  resting state  (1), sodium and potassium ions have limited ability to pass through the membrane, and the neuron has a net negative charge inside. Once the action potential is triggered, the  depolarization  (2) of the neuron activates sodium channels, allowing sodium ions to pass through the cell membrane into the cell, resulting in a net positive charge in the neuron relative to the extracellular fluid. After the action potential peak is reached, the neuron begins  repolarization  (3), where the sodium channels close and potassium channels open, allowing potassium ions to cross the membrane into the extracellular fluid, returning the membrane potential to a negative value. Finally, there is a  refractory period  (4), during which the voltage-dependent ion channels are  inactivated  while the Na +  and K +  ions return to their resting state distributions across the membrane (1), and the neuron is ready to repeat the process for the next action potential.


When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of  neurotransmitter  molecules that open ion channels in the post-synaptic neuron (bottom). The combined  excitatory  and  inhibitory postsynaptic potentials  of such inputs can begin a new action potential in the post-synaptic neuron.


In  pacemaker potentials , the cell spontaneously depolarizes (straight line with upward slope) until it fires an action potential.


In  saltatory conduction , an action potential at one  node of Ranvier  causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node.


Comparison of the  conduction velocities  of myelinated and unmyelinated  axons  in the  cat . [ 55 ]  The conduction velocity  v  of myelinated neurons varies roughly linearly with axon diameter  d  (that is,  v  ∝  d ), [ p ]  whereas the speed of unmyelinated neurons varies roughly as the square root ( v  ∝ √ d ). [ u ]  The red and blue curves are fits of experimental data, whereas the dotted lines are their theoretical extrapolations.


Cable theory's simplified view of a neuronal fiber. The connected  RC circuits  correspond to adjacent segments of a passive  neurite . The extracellular resistances  r e  (the counterparts of the intracellular resistances  r i ) are not shown, since they are usually negligibly small; the extracellular medium may be assumed to have the same voltage everywhere.


Electrical synapses  between excitable cells allow ions to pass directly from one cell to another, and are much faster than  chemical synapses .


Phases of a cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive  calcium  channels.


Giant axons of the longfin inshore squid ( Doryteuthis pealeii ) were  crucial for scientists  to understand the action potential. [ 73 ]


As revealed by a  patch clamp  electrode, an  ion channel  has two states: open (high conductance) and closed (low conductance).


Tetrodotoxin  is a lethal toxin found in  pufferfish  that inhibits the  voltage-sensitive sodium channel , halting action potentials.


Image of two  Purkinje cells  (labeled as  A ) drawn by  Santiago Ramón y Cajal  in 1899. Large trees of  dendrites  feed into the  soma , from which a single  axon  emerges and moves generally downwards with a few branch points. The smaller cells labeled  B  are  granule cells .


Ribbon diagram  of the sodium–potassium pump in its E2-Pi state. The estimated boundaries of the  lipid bilayer  are shown as blue (intracellular) and red (extracellular) planes.


Equivalent electrical circuit for the Hodgkin–Huxley model of the action potential.  I m  and  V m  represent the current through, and the voltage across, a small patch of membrane, respectively. The  C m  represents the capacitance of the membrane patch, whereas the four  g 's  represent the  conductances  of four types of ions. The two conductances on the left, for potassium (K) and sodium (Na), are shown with arrows to indicate that they can vary with the applied voltage, corresponding to the  voltage-sensitive ion channels . The two conductances on the right help determine the  resting membrane potential .


The action of the  sodium-potassium pump  is an example of primary active transport.


Function of  symporters  and  antiporters .


Cellular mechanisms of early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs).


Schematic of an  electrophysiological  recording of an action potential, showing the various phases that occur as the voltage wave passes a point on a cell  membrane . The afterhyperpolarisation is one of the processes that contribute to the refractory period.


Amphipathic Lipid Packing Sensor motifs of proteins associate with ( adsorb  to) curved lipid bilayers. [ 5 ]


Structure of gram-negative cell envelope


An illustration depicting diversity in the architecture of protein secretion systems found in  diderm bacteria [ 1 ]


T1SS schematic


T2SS schematic


T3SS schematic


T4SS schematic


T5SS schematic


ESX-5: type VII secretion system, Mycobacterium xenopi


Type IX secretion system schematic diagram [ 38 ]


Staphylococcus aureus  biofilm on an indwelling  catheter


Probable  cyanobacteria  in the vertical section of a silicified biofilm from the Lower Cretaceous. Very shallow hypersaline environment of the  Urgonian   carbonate platform  of Provence, south eastern France.


Biofilm of golden  hydrophobic   bacteria ; ceiling of Golden Dome Cave, a  lava tube  in  Lava Beds National Monument [ 20 ]


Mature biofilm structure   [ 25 ]  Biofilm is characterised by heterogenous environment and the presence of a variety of subpopulations. A biofilm structure is composed of metabolically active (both resistant and tolerant) and non-active cells (viable but not culturable cells and persisters) as well as polymer matrix consisting of polysaccharide, extracellular DNA and proteins. Biofilm growth is associated with an escalated level of mutations and  horizontal gene transfer  which is promoted in due to the packed and dense structure. Bacteria in biofilms communicate by  quorum sensing , which activates genes participating in virulence factors production. [ 25 ] [ 26 ]


Five stages of biofilm development   [ 28 ]  (1) Initial attachment, (2) Irreversible attachment, (3) Maturation I, (4) Maturation II, and (5) Dispersion. Each stage of development in the diagram is paired with a  photomicrograph  of a developing  P. aeruginosa  biofilm. All photomicrographs are shown to the same scale.


Biofilm dispersal


Scanning electron micrograph of mixed-culture biofilm, demonstrating in detail a spatially heterogeneous arrangement of bacterial cells and extracellular polymeric substances.


Mats of bacterial biofilm color the hot springs in  Yellowstone National Park . The longest raised mat area is about half a meter long.


Thermophilic bacteria in the outflow of  Mickey Hot Springs ,  Oregon , approximately 20 mm thick.


A biofilm from the  Dead Sea


Transmission electron micrograph showing bacteria Escherichia coli that form extensive biofilms using a network of conjugative F-pili. Source: Jonasz Patkowski


Cardiolipin in animal tissues


Cardiolipin synthesis in eukaryotes


Respiratory electron transfer of Complex IV


The mechanism whereby CL triggers apoptosis


CL serves as a proton trap in oxidative phosphorylation


Leica  confocal microscope systems


Anaerobic experiment station


CBE Industrial Associates as of Nov. 1, 2021.


Diagram of a crenated leaf


In (d) the RBCs are rendered crenated from a  hypertonic  solution


A  mitochondrion , with labeled cristae.


An example of the role of cyclic nucleotide–gated ion channels in  sea urchin  sperm chemotaxis.


Cyclic adenosine monophosphate


Cyclic guanosine monophosphate


Illustration of a cyclic nucleotide–gated ion channel with a cAMP binding domain.


Fundus of patient with retinitis pigmentosa, mid stage (Bone spicule-shaped pigment deposits are present in the mid periphery along with retinal atrophy, while the macula is preserved although with a peripheral ring of depigmentation. Retinal vessels are attenuated.)


CryoEM Structure of a prokaryotic cyclic nucleotide-gated ion channel.


Blood cells in solutions with different osmotic pressure. Cytolysis would result in the image on the far right.


Micrographs of osmotic pressure on red blood cells


Entry of material into the nucleus through endocytosis. Endocytosis: The membrane of the cell invaginates, creating a small circular pit that is taken into the cytosol of the cell. This circular membrane coated pit is a vesicle that is transported to the  lysosome  of the cell to be degraded by enzymes.


Mechanism of clathrin-dependent endocytosis. Clathrin-coated pits in endocytosis: The membrane of the cell invaginates using the protein clathrin. The clathrin uses actin to pull together the sides of the plasma membrane and form a vesicle inside the cellular cytosol.


Exocytosis (L) and Endocytosis (R)


Action potential  in a  neuron , showing depolarization, in which the cell's internal charge becomes less negative (more positive), and repolarization, where the internal charge returns to a more negative value.


Voltage-gated sodium channel . Open channel  (top)  carries an influx of Na +  ions, giving rise to depolarization. As the channel becomes closed/inactivated  (bottom) , the depolarization ends.


Structure of a neuron


Summation  of stimuli at an  axon hillock


Electrocardiogram


Figure 1. Drug flux diagram


Protein TolC, the outer membrane component of a tripartite efflux pump in  Escherichia coli .


AcrB, the other component of pump,  Escherichia coli .


An example of a phosphatidylcholine, a type of phospholipid in egg lecithin. Red - choline and phosphate group; Black - glycerol; Green - unsaturated fatty acid; Blue - saturated fatty acid


Diagram of ion concentrations and charge across a semi-permeable cellular membrane.


Diagram of the Na + -K + -ATPase.


Diagram of the conformational shift in retinal that initiates proton pumping in bacteriorhodopsin.


Simplified diagram of photophosphorylation.


Detailed diagram of the electron transport chain in mitochondria.


Examples of electrotonic potentials


Equivalent circuit  of a neuron constructed with the assumptions of simple cable theory.


Poster on ethosomes


Exocytosis of neurotransmitters into a synapse from neuron A to neuron B.  Mitochondrion Synaptic vesicle  with  neurotransmitters Autoreceptor Synapse  with neurotransmitter released ( serotonin ) Postsynaptic receptors activated by neurotransmitter (induction of a postsynaptic potential) Calcium channel Exocytosis of a vesicle Recaptured neurotransmitter


Molecular machinery driving exocytosis in neuromediator release. The core SNARE complex is formed by four α-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a calcium sensor and regulates intimately the SNARE zipping. [ 11 ]


In the lipid-lined pore theory, both membranes curve toward each other to form the early fusion pore.  When the two membranes are brought to a "critical" distance, the lipid head-groups from one membrane insert into the other, creating the basis for the fusion pore.


Extracellular polymeric substance matrix formation in a  biofilm


Succinoglycan from  Sinorhizobium meliloti


Shadowed electron micrograph of unaligned phage


Assembled major coat protein, exploded view


Schematic views showing minor proteins at the two ends


Diagram of the alkaline mucous layer in the stomach with mucosal defense mechanisms


The general structure of the intestinal wall


Image of the mucosa of the  stomach , showing an epithelium (at top, and also facing the elongated cavities) made up of  column-shaped cells .


Muscular layers of the  stomach  wall.


Membrane structures.  Top , an archaeal phospholipid:  1 , isoprene chains;  2 , ether linkages;  3 ,  L-glycerol   moiety ;  4 , phosphate group.  Middle , a bacterial or eukaryotic phospholipid:  5 , fatty acid chains;  6 , ester linkages;  7 ,  D-glycerol  moiety;  8 , phosphate group.  Bottom :  9 , lipid bilayer of bacteria and eukaryotes;  10 , lipid monolayer of some archaea.


General pathways for GPCR homologous desensitization


Some representative hopanoids: A. Diploptene, also called 22(29)-hopene  B. Diplopterol, also called hopan-22-ol, the hydrated cyclomer of diploptene  C. Bacteriohopanetetrol (BHT), a common extended hopanoid  D. Hopane, the diagenetic product of A and B that results from reducing conditions during deposition and persists in the rock record. The diagenetic product of C would be an extended C 35  hopane.


Active site of the squalene-hopene cyclase from  Methylococcus capsulatus  engaging the substrate, squalene, shown in gold. The cyclase is depicted as a monomer.


Alpha barrel structure of the squalene-hopene cyclase from  Methylococcus capsulatus . Alpha helices are shown in blue, loop regions in green, and beta sheets in red.


Structure of a 2-α-methylhopane with the carbons of the base hopane structure numbered according to convention. The methyl group at the C 2  position is indicated in red.


Hydrophobic Mismatch.


Mattress model


Diagram of membrane potential changes during an action potential


The  (a)  resting membrane potential is a result of different concentrations of Na +  and K +  ions inside and outside the cell. A nerve impulse causes Na +  to enter the cell, resulting in  (b)  depolarization. At the peak action potential, K +  channels open and the cell becomes  (c)  hyperpolarized.


This image shows a model of a patch clamp used in neuroscience. The pipette tip is placed at an ion channel opening and a current is applied and measured using a voltage clamp.


An example of inhibitory postsynaptic potentials (IPSPs), excitatory postsynaptic potentials (EPSPs), and their summation.


Biofilms in marine environments  Various biofilm components (including bacteria, algae, and fungi) are embedded in a matrix of extracellular polymeric substances.


Stages of biofilm development    1) Initial Attachment 2) Irreversible Attachment 3) Maturation I 4) Maturation II 5) Dispersion.


Scanning electron micrograph of mixed-culture biofilm, showing the arrangement of bacterial cells and extracellular polymeric substances


Various types of interactions within the biofilm (1) Communication through quorum sensing (2) Adaptations to varying conditions such as light


Nutrient cycling in the marine environment


Carrier and channel ionophores  (a) Carrier ionophores reversibly bind ions and carry them through cell membranes.  (b) Channel ionophores create channels within cell membranes to facilitate the transport of ions.


The structure of the complex of sodium (Na + ) and the antibiotic  monensin A


Structure of a potassium complex of a  crown ether , a synthetic ionophore-ion complex


The three main structures phospholipids form in solution; the  liposome  (a closed bilayer), the micelle and the bilayer.


Immunohistochemical analysis of L-type calcium channel  Cav1.3  (CACNA1D) in human  adrenal cortex . Marked immunoreactivity was detected in the  zona glomerulosa . In the figure: ZG = zona glomerulosa, ZF =  zona fasciculata , AC = adrenal capsule.  Immunohistochemistry  was performed according to published methods. [ 1 ]


An L-type calcium channel with its subunits labeled along with some drugs known to inhibit the channel.


Alpha subunit of a generic voltage-gated ion channel


Figure 1 Multi-lamellar phase of aqueous lipid dispersions, each white lamella represents a  lipid bilayer  organization in  liposome  made by vortex-mixing of dried total lipid extract of spinach  thylakoid  membranes with distilled water. Phosphotungstic acid  negative stained  sample viewed with  transmission electron microscopy  technique.


A schematic of a lamellar structure for a  eutectic system


Ion-channel-linked receptor Ions Ligand  (such as  acetylcholine )  When ligands bind to the receptor, the  ion channel  portion of the receptor opens, allowing ions to pass across the  cell membrane .


Nicotinic acetylcholine receptor in closed state with predicted membrane boundaries shown, PDB 2BG9


The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2


AMPA receptor trafficking


Stylized depiction of an activated NMDAR


Figure 1. Schematic representation showing the membrane topology of a typical P2X receptor subunit. First and second transmembrane domains are labeled TM1 and TM2.


Lipid membrane with various proteins


Isoprene unit


Caax Box


Prenylation chains (e.g.  geranyl pyrophosphate )


Myristoylation


Palmitoylation


Structure of the glycophosphatidylinositol anchor in the plasma membrane of a eukaryotic cell


This fluid  lipid  bilayer cross section is made up entirely of  phosphatidylcholine .


The three main structures phospholipids form in solution; the  liposome  (a closed bilayer), the micelle and the bilayer. [ 1 ]


Schematic cross sectional profile of a typical lipid bilayer. There are three distinct regions: the fully hydrated headgroups, the fully dehydrated alkane core and a short intermediate region with partial hydration. Although the head groups are neutral, they have significant dipole moments that influence the molecular arrangement. [ 5 ]


TEM  image of a bacterium. The furry appearance on the outside is due to a coat of long-chain sugars attached to the cell membrane. This coating helps trap water to prevent the bacterium from becoming dehydrated.


Diagram showing the effect of unsaturated lipids on a bilayer. The lipids with an unsaturated tail (blue) disrupt the packing of those with only saturated tails (black). The resulting bilayer has more free space and is, as a consequence, more permeable to water and other small molecules.


Illustration of a GPCR signaling protein. In response to a molecule such as a  hormone  binding to the exterior domain (blue) the GPCR changes shape and  catalyzes  a chemical reaction on the interior domain (red). The gray feature is the surrounding bilayer.


Transmission Electron Microscope  (TEM) image of a  lipid vesicle . The two dark bands around the edge are the two leaflets of the bilayer. Historically, similar images confirmed that the cell membrane is a bilayer


Human red blood cells viewed through a fluorescence microscope. The  cell membrane  has been stained with a fluorescent dye. Scale bar is 20μm.


3d-Adapted  AFM  images showing formation of transmembrane pores (holes) in supported lipid bilayer [ 55 ]


Illustration of a typical  AFM  scan of a supported lipid bilayer. The pits are defects in the bilayer, exposing the smooth surface of the substrate underneath.


Structure of a potassium ion channel. The  alpha helices  penetrate the bilayer (between red and blue lines), opening a hole through which potassium ions can flow


Schematic illustration of pinocytosis, a type of endocytosis


Exocytosis of outer membrane vesicles (MV) liberated from inflated periplasmic pockets (p) on surface of human  Salmonella  3,10:r:- pathogens docking on plasma membrane of macrophage cells (M) in chicken ileum, for host-pathogen signaling  in vivo .


Schematic showing two possible conformations of the lipids at the edge of a pore. In the top image the lipids have not rearranged, so the pore wall is hydrophobic. In the bottom image some of the lipid heads have bent over, so the pore wall is hydrophilic.


Illustration of lipid vesicles fusing showing two possible outcomes: hemifusion and full fusion. In hemifusion, only the outer bilayer leaflets mix. In full fusion both leaflets as well as the internal contents mix.


Schematic illustration of the process of fusion through stalk formation.


Diagram of the action of SNARE proteins docking a vesicle for exocytosis. Complementary versions of the protein on the vesicle and the target membrane bind and wrap around each other, drawing the two bilayers close together in the process. [ 92 ]


Human red blood cells viewed through a microscope. The  cell membrane  has been stained with a fluorescent dye. Scale bar is 20 μm.


Patch clamp  recordings of changes in conductivity associated with the opening and closing of an  ion channel .


Image from a Transmission Electron Microscope of a lipid vesicle. The two dark bands around the edge are the two leaflets of the bilayer. Similar electron micrographs confirmed the bilayer nature of the cell membrane in the 1950s


Illustration of lipid vesicles fusing showing two possible outcomes: hemifusion and full fusion. In hemifusion only the outer bilayer leaflets mix. In full fusion both leaflets as well as the internal contents mix.


Diagram of the action of SNARE proteins docking a vesicle for exocytosis. Complementary versions of the protein on the vesicle and the target membrane bind and wrap around each other, drawing the two bilayers close together in the process. [ 15 ]


(1.) Illustration of lipid mixing assay based on Förster resonance energy transfer.


(3.) Illustration of lipid mixing assay based on Fluorescence self-quenching.


(1.) Illustration of content mixing assay based on fluorescence quencing pair ANTS/DPX.


(2.)Illustration of content mixing assay based on fluorescence enhancement pair Tb 3+ /DPA.


Cross section view of the structures that can be formed by phospholipids in aqueous solutions


Diagram showing the effect of unsaturated lipids on a bilayer. The lipids with an unsaturated tail (blue) disrupt the packing of those with only saturated tails (black). The resulting bilayer has more free space and is consequently more permeable to water and other small molecules.


The chemical structure of cholesterol, which differs greatly from a standard phospholipid.


Example of lipid polymorphism as bilayer (le), reverse spherical micelles (M) and reverse hexagonal cylinders H-II phase (H) in negatively stained transmission electron micrograph of spinach thylakoid lipid-water dispersions.


Lipid raft organization, region (1) is a standard lipid bilayer, while region (2) is a lipid raft.


Space-filling models of sphingomyelin (a) and cholesterol (b)


Components for IgE signalling


IgE signalling process


Components for T-cell antigen receptor signalling


T-cell antigen receptor signalling process


The lipidome (in yellow) as a part of the  metabolome  and the total  interactome  of a cell.


Scheme of a liposome formed by  phospholipids  in an  aqueous  solution.


Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease. [ 1 ]


Seven main categories for liposomes: multilamellar large (MLV), oligolamellar (OLV), small unilamellar (SUV), medium-sized unilamellar (MUV), large unilamellar (LUV), giant unilamellar (GUV) and multivesicular vesicles (MVV)) [ 7 ] .


A micrograph of phosphatidylcholine liposomes, which were stained with  fluorochrome   acridine orange . Method of  fluorescence  microscopy (1250-fold magnification).


Various types of phosphatidylcholine liposomes in suspension. Method of  phase-contrast microscopy  (1000-fold magnification).   The following types of liposomes are visible: small monolamellar vesicles, large monolamellar vesicles, multilamellar vesicles, oligolamellar vesicles.


Pictorial representation of targeted theranostics liposomal delivery


Schematic of a monolamellar liposome.


The originally published TM topology of the CorA protein


The TM topology of the MgtB protein


The predicted TM topology of the MgtE protein


The TM topology of the MRS2 and LPE10 proteins


The TM topology of the XNTA protein


The predicted TM topology of MgtE from  H. sapiens


The predicted TM topology of the TRPM6 and TRPM7 proteins


The predicted TM topology of the AtMHX protein


Gating Mechanism of MS.Stretch activated model, tension in the lipid bilayer triggers conformational changes which open the channel. Figure adapted from Lumpkin et al. [ 67 ]


Gating Mechanism of MSC:Spring-like tether model - The tethers are attached to the channel proteins and are connected to the cytoskeleton. The tethers act like spring mechanisms of a shutter. Figure adapted from Lumpkin et al. [ 67 ]


The closed structure of MscS


The closed structure of MscL


Finite Element Model of MscL, a bacterial channel. This figure is similar to that in Tang et al. [ 94 ]


Curvature radii


Different changes to lipid structure, such as tail saturation, affect the overall shape of the lipid. A change in shape such as the one shown, when disproportionately in higher concentration on one side of the membrane, allows the membrane to curve.


Transmembrane proteins with inherent curvature inducing curvature in a membrane.


Insertion of a piece of a protein into one leaflet of the membrane induces curvature.


A BAR domain of a protein inducing and stabilizing the curvature of a membrane.


Cage-like structure of  clathrin . When this structure forms around a membrane, it pulls the membrane into a tight curvature until eventual vesicle budding.


Cytoskeletal structure inducing membrane curvature. The inherent shape of a cell - as controlled by its cytoskeleton - requires that the bilayer membrane curve around it.


This figure illustrates membrane bending caused by protein crowding. When a high local concentration of proteins (shown in green) are present on the membrane surface (shown in black), membrane curvature can be induced. This hypothesis reasoned that the high protein concentration increases the likelihood of repulsions between proteins, therefore generates steric pressure between proteins. To relieve such pressure, lipid membrane has to bend in order to decrease protein repulsions.


The major membrane lipids PtdCho  -  Phosphatidylcholine ;  PtdEtn  -  Phosphatidylethanolamine ;  PtdIns  -  Phosphatidylinositol ;  PtdSer  -  Phosphatidylserine .


Space-filling models of (a) sphingomyelin and (b) cholesterol.


Diagram of the arrangement of amphipathic lipid molecules to form a  lipid bilayer . The yellow  polar  head groups separate the grey hydrophobic tails from the aqueous cytosolic and extracellular environments.


Singer and Nicolson's fluid mosaic model


Transient receptor potential cation channel subfamily V member 1 ( TRPV1 ).  Ion channels  are integral membrane proteins of great importance for living organisms.


Key :  Blue  pentagons – sodium ions;  Purple  squares – potassium ions;  Yellow  circles – chloride ions;  Orange  rectangles – membrane-impermeable anions (these arise from a variety of sources including proteins).   The large  purple  structure with an arrow represents a transmembrane potassium channel and the direction of net potassium movement.


Electric field (arrows) and contours of constant voltage created by a pair of oppositely charged objects. The electric field is at right angles to the voltage contours, and the field is strongest where the spacing between contours is the smallest.


Ions (pink circles) will flow across a membrane from the higher concentration to the lower concentration (down a concentration gradient), causing a current. However, this creates a voltage across the membrane that opposes the ions' motion. When this voltage reaches the equilibrium value, the two balance and the flow of ions stops. [ 5 ]


The cell membrane, also called the plasma membrane or plasmalemma, is a  semipermeable  lipid bilayer common to all living cells. It contains a variety of biological molecules, primarily proteins and lipids, which are involved in a vast array of cellular processes.


Facilitated diffusion in cell membranes, showing ion channels and  carrier proteins


The sodium-potassium pump uses energy derived from ATP to exchange sodium for potassium ions across the membrane.


Despite the small differences in their radii, [ 17 ]  ions rarely go through the "wrong" channel. For example, sodium or calcium ions rarely pass through a potassium channel.


Depiction of the open potassium channel, with the potassium ion shown in purple in the middle, and hydrogen atoms omitted. When the channel is closed, the passage is blocked.


Ligand-gated calcium channel in closed and open states


Equivalent circuit for a patch of membrane, consisting of a fixed capacitance in parallel with four pathways each containing a battery in series with a variable conductance


Reduced circuit obtained by combining the ion-specific pathways using the  Goldman equation


Graph displaying an EPSP, an IPSP, and the summation of an EPSP and an IPSP


Group I and II transmembrane proteins have opposite final topologies.    Group I proteins have the N terminus on the far side and C terminus on the cytosolic side.    Group II proteins have the C terminus on the far side and N terminus in the cytosol. However final topology is not the only criterion for defining transmembrane protein groups, rather location of topogenic determinants and mechanism of assembly is considered in the classification [ 2 ]


Diagram of a  cell membrane        1. phospholipid    2. cholesterol    3. glycolipid    4. sugar    5. polytopic protein (transmembrane protein)     6. monotopic protein (here, a glycoprotein)    7. monotopic protein anchored by a phospholipid    8. peripheral monotopic protein (here, a glycoprotein.)


Transport of substances across the plasma membrane can be via passive transport (simple and facilitated diffusion) or active transport.


[ 6 ]  A  semipermeable membrane  separates two compartments of different solute concentrations: over time, the solute will diffuse until equilibrium is reached.


Uniport, symport, and antiport of molecules through membranes.


Simplified diagram of a  sodium potassium pump  showing alpha and beta units.


Here a vesicle forms as cargo, receptors and coat proteins gather. The vesicle then buds outwards and breaks free into the cytoplasm. The vesicle is moved towards its target location then docks and fuses.


Fig. 2  Membrane vesicle trafficking  Mechanism (A–E), proposed for release (stages A–C) of outer membrane vesicles, OMVs from gram-negative bacteria in analogy of soap-bubble formation from a bubble-tube assembly (RC in stage C) of rivet complexes, RC, and their translocation (stage D) to animal host/target cell, TC. General secretory pathway (GSP) secretes proteins across bacterial cell membrane (CM) to bulge out lipopolysaccharide (LPS)-rich outer membrane (OM) above peptidoglycan (PDG) layer into pockets of inflated periplasm, called periplasmic organelles (PO) to pinch off OMVs containing outer membrane proteins (OMPs), secretory proteins (SP) and chaperons (CH). OMVs signal epithelial host cells (EHC) to ruffle (R) aiding macropinoctosis of gram negative (G−) microbe (stage E).


Fig. 3 Transmission electron micrograph of human  Salmonella  organism bearing periplasmic organelles, (p, line arrow) on its surface and releasing bacterial outer membrane vesicles (MV) being endocytosed (curved arrow) by macrophage cell (M) in chicken ileum  in vivo


Anesthetic (orange) is shown competing with the palmitates (blue) of a palmitoylated protein (green). The displacement of the protein from the ordered lipids in the membrane (grey) renders the protein anesthetic sensitivity. The palmitate site is selective and structured similar to a protein despite being composed of lipids.


Mesosomes form in bacterial cells prepared for  electron microscopy  by chemical fixation, but not by freeze-fracture fixation. [ 1 ]


Cross-section view of the structures that can be formed by phospholipids in aqueous solutions (unlike this illustration, micelles are usually formed by single-chain lipids, since it is difficult to fit two chains into this shape)


Scheme of a micelle formed by  phospholipids  in an  aqueous  solution


Electron micrograph of the windmill-like supermicelle, scale bar 500 nm [ 20 ]


The great plate count anomaly. Counts of cells obtained via cultivation are orders of magnitude lower than those directly observed under the microscope. This is because microbiologists are able to cultivate only a minority of naturally occurring microbes using current laboratory techniques, depending on the environment. [ 1 ]


Louis Pasteur


Juxtaposition between  endoplasmic reticulum  (ER) and  mitochondria  via MAM


Models of the role of  contacts  between mitochondria and ER in apoptosis


Schematic of a painted bilayer experiment. A sheet of plastic with a small hole in the center separates the two sides of the chamber. The bilayer is formed across this hole, separating the two chambers. The electrical properties of the bilayer can be measured by putting an electrode into each side of the chamber.


Diagram of a supported bilayer


Fluorescence micrograph of a supported bilayer on a substrate that has been patterned with a corral. This substrate was then sequentially exposed to two different populations of lipids (dyed red and green). Although the populations were kept largely separated there was some intermixing at the interface as seen from the color gradient.


Diagram showing formation of t-BLM.


Diagram of lipid vesicles showing a solution of molecules (green dots) trapped in the vesicle interior.


Chemical structure of MLCL backbone


Schematic illustration of a MSP nanodisc with a  7-transmembrane  protein embedded. Diameter is about 10 nm. Picture from Sligar Lab


Neurophysin II protein domain unbound to vasopressin


Neurophysin-Oxytocin complex


Schematic representation of a niosome prepared by sorbitan monostearate (Span-60) [ 1 ]


Node of Ranvier in the  peripheral nervous system


Nodes of Ranvier in the Central and Peripheral Nervous Systems


Louis Antoine Ranvier (1835–1922)


A volumetric surface render (red) of the nuclear envelope of one  HeLa cell . The cell was observed in 300 slices of  electron microscopy , the nuclear envelope was automatically segmented and rendered. One vertical and one horizontal slice are added for reference.


Nuclear pores crossing the nuclear envelope


Breakdown and reassembly in  mitosis


The Ran-GTP cycle, which drives the import and export of RNA and proteins through the nuclear protein complex.


Scanning and illumination microscopy of nuclear pores,  lamina , and  chromatin .


Cell nucleus containing nuclear pores.


Figure from original paper, showing line diagrams of phagosomes arising from omegasomes (part D).


Illustration showing steps from omegasome to autolysosome. [ 5 ]


Movement of water and ions in freshwater fish


Movement of water and ions in saltwater fish


Protist  Paramecium  aurelia  with contractile vacuoles.


Osmosis in a U-shaped tube


A  Pfeffer cell  used for early measurements of osmotic pressure


Osmotic pressure on red blood cells


This caption is not  succinct .  Please  improve this article  if you can.   ( July 2017 )  Transmission electron micrograph of outer membrane vesicles (OMV) (size 80–90 nm, dia) released by human pathogen  Salmonella  3,10:r:- in chicken ileum,  in vivo . OMVs were proposed to be 'blown off' from large bacterial periplasmic protrusions, called  periplasmic organelles  (PO) with the help of 'bubble tube'-like assembly of about four  type III secretion  injectisomal  rivet complexes  (riveting bacterial outer and cell membrane to allow pockets of periplasm to expand into POs). This allows  membrane vesicle trafficking  of OMVs from gram negative bacteria to dock on host epithelial cell membrane (microvilli), proposed to translocate signal molecules from pathogen to host cells at the  host–pathogen interface .


Passive diffusion across a  cell membrane .


Passive diffusion on a cell membrane.


Depiction of facilitated diffusion.


Filtration.


Effect of osmosis on blood cells under different solutions.


Vat Red 29  typical example of a structure with a perylene core


Biosynthesis of various phospholipids (including phosphatidylethanolamine) in bacteria


The major  membrane lipids :   phosphatidylcholine  (PtdCho);  phosphatidylethanolamine (PtdEtn);   phosphatidylinositol  (PtdIns);   phosphatidylserine  (PtdSer).


Ethanolamine


General chemical structure of a phosphatidyl glycerol where R 1  and R 2  are fatty acid side chains


Biosynthesis of Phosphatidylglycerol


Depicting the process of hydrolysis and biosynthesis at the plasma membrane and Endoplasmic Reticulum (ER). Describing the cycle of PI, with respective enzymatic processes and reactions.                                       Made by Mathias Sollie Sandsdalen in BioRender.com, modified from N.J. Blunsom and S. Cockcroft. [ 20 ]


Biosynthesis of phosphatidylserine


The names, Drosophila homologs, and domain architecture of the PITPNM family proteins.


Nir1 localizes to ER-PM MCS using its FFAT and LNS2 domains. It is thought to directly interact with Nir2 in order to recruit Nir2 to the ER-PM MCS, so that Nir2 can transfer lipids with its PITP domain.


Plant cell undergoing Plasmolysis in a Hypertonic solution (x400 magnification)


Plant cell under different environments


PNGase F cleavage sites.


PNGase F cleaves glycan and deaminates asparagine to aspartic acid.


Polarized membrane due to inward and outward movement of ions


Skeletal formula of the prenyl group.


The three main structures phospholipids form in solution: the  liposome  (a closed bilayer), the micelle and the bilayer.


Scheme of a  micelle  spontaneously formed by  phospholipids  in an  aqueous  solution


Schematic showing two possible conformations of the lipids at the edge of a pore. In the top image the lipids have not rearranged, so the pore wall is hydrophobic. In the bottom image some of the lipid heads have bent over, so the pore wall is hydrophilic.


This fluid  lipid  bilayer cross section is made up entirely of  phosphatidylcholine .


Surfactant molecules arranged on an air–water interface


Protoplasts of cells from a petunia's leaf


Protoplasts of the moss  Physcomitrella patens


Fused protoplast (on left), containing both chloroplasts (from a leaf cell) as well as a  coloured vacuole (from a petal).


Structure schematic, showing sugar units and UDP-L-Glu-γ-L-Ala-ε-L-Lys-L-Ala peptide stem. Additional glutamic acid residue attached to the L-Lys residue via a γ bond [ 1 ]  not shown.


Pterygium of the eye


An example of membrane  receptors .  Ligands, located outside the cell Ligands connect to specific receptor proteins based on the shape of the active site of the protein. The receptor releases a messenger once the ligand has connected to the receptor.


Transmembrane receptor: E=extracellular space; I=intracellular space; P=plasma membrane


Efficacy spectrum of receptor ligands.


A labeled diagram of an  action potential . As seen above, repolarization takes place just after the peak of the action potential, when  K +  ions rush out of the cell.


The  Na + /K + -ATPase , as well as effects of diffusion of the involved ions, are major mechanisms to maintain the resting potential across the membranes of animal cells.


A diagram showing the progression in the development of a membrane potential from a concentration gradient (for potassium).  Green  arrows indicate net movement of K +  down a concentration gradient.  Red  arrows indicate net movement of K +  due to the membrane potential. The diagram is misleading in that while the concentration of potassium ions outside of the cell increases, only a small amount of K +  needs to cross the membrane in order to produce a membrane potential with a magnitude large enough to counter the tendency of the potassium ions to move down the concentration gradient.


Embedded cylindrical object of radius

 a

 {\displaystyle a}

  in a membrane with viscosity

 η

 m

 {\displaystyle \eta _{m}}

 , height

 h

 {\displaystyle h}

 , surrounded by bulk fluid with viscosity

 η

 f

 {\displaystyle \eta _{f}}


Schematic of semipermeable membrane during  hemodialysis , where blood is red, dialysing fluid is blue, and the membrane is yellow.


Salt outside of the cell creates osmotic pressure that pushes water through the phospholipid bilayer


Dialysis tubing allows waste molecules to be selectively removed from blood.


Serous membrane lines the pericardial cavity and reflects back to cover the heart—much the same way that an underinflated balloon would form two layers surrounding a fist. [ 1 ]


Schematic diagram of an organ invaginating into a serous cavity


Compounds of SkQ


Fig 1. The vesicle fusion complex. The vesicle approaches the membrane and proteins including SNAP, NSF, synaptobrevin, syntaxin, and synaptotagmin SNARE proteins form the 20S SNARE Complex required for fusion. The ATPase action of NSF drives disassembly post priming of the complex. Ca 2+  influx due to depolarization drives vesicle fusion to the membrane and release of neurotransmitters.


Action of botulinum toxin at the synaptic nerve terminals interferes with the assembly of the 20S SNARE complex and prevents the signaling.


General structures of  sphingolipids


Sphingomyelin Black:  Sphingosine Red:  Phosphocholine Blue:  Fatty acid


Top-down view of sphingomyelin, demonstrating its nearly cylindrical shape


Sphingomyelin de novo synthesis pathway


Simplified cross-section of a mitochondrion and a submitochondrial particle, showing the particle's inverted membrane orientation. Whereas whole submitochondrial particles can perform oxidative phosphorylation yielding ATP, destabilized particles lacking F 1  particles consume oxygen and oxidize NADH without synthesizing ATP, and free F 1  particles catalyze the hydrolysis of ATP into ADP.


Structures of general anaesthetics widely used in medicine. [ 1 ]  1 -  ethanol , 2 -  chloroform , 3 -  diethyl ether , 4 -  fluroxene , 5 -  halothane , 6 -  methoxyflurane , 7 -  enflurane , 8 -  isoflurane , 9 -  desflurane , 10 -  sevoflurane


The Meyer-Overton correlation for anaesthetics


As bulky and hydrophobic anaesthetic molecules accumulate inside the neuronal cell membrane, this causes membrane distortion and expansion (thickening) due to volume displacement. Membrane thickening reversibly alters function of membrane ion channels thus providing anaesthetic effect. The actual chemical structure of the anaesthetic agent  per se  was not important, but its molecular volume plays the major role: the more space within membrane is occupied by anaesthetic, the greater is the anaesthetic effect.


Anesthetic (orange) is shown competing with the palmitates (blue) of a palmitoylated protein (green). The displacement of the protein from the ordered lipids in the membrane (grey) renders the protein anesthetic sensitivity. The palmitate site is selective and structured similarly to a protein despite being composed of lipids


General anaesthetic changes membrane lateral pressure profile which determines conformation of membrane ion channel (green lock)


Inhaled general anaesthetics frequently do not change structure of their target protein (of Cys-loop receptor here) but change its dynamics especially dynamics in the flexible loops that connect α-helices in a bundle thus disrupting modes of motion essential for the protein function.


GABA A  receptor and where various ligands bind.


The Meyer-Overton rule predicts the constant increase of anaesthetic potency of n-alkanols with increasing chain length. However, above certain length the potency vanishes.


A)  Short hydrocarbon chains are relatively rigid in terms of conformational enthropy and are close to alkanol hydroxyl group ("buoy") tethered to the interface. This makes short chain alkanols efficient mediators that redistribute lateral stress from membrane interior to its interface.  B)  This ability decreases in the row of n-alkanols since longer chains are more flexible and are not so tightly tethered to the hydroxyl group.  C)  Polyhydroxyalkanes 1,6,11,16-hexadecanetetraol and 2,7,12,17-octadecanetetraol exhibit significant anaesthetic potency as was predicted by cutoff effect because the length of the hydrocarbon chain between hydroxyl groups is smaller than the cutoff.


Thylakoids (dark green) inside a chloroplast


Thylakoid structures


Scanning transmission electron microscope (STEM) imaging of thylakoid membranes  10-nm-thick STEM tomographic slice from a lettuce chloroplast. Grana stacks are interconnected by unstacked stromal thylakoids, called  stroma lamellae . Scalebar = 200 nm. See. [ 2 ]


Granum-stroma assembly structure  The prevailing model of the granum-stroma assembly is stacks of granal thylakoids wrapped by right-handed helical stromal thylakoids which are connected to large parallel sheets of stromal thylakoids and adjacent right-handed helices by left-handed helical structures. (Based on  [ 2 ] ).


Thylakoid disc with embedded and associated proteins.


Schematic representation of thylakoid protein targeting pathways. [ 29 ]


Light-dependent reactions of photosynthesis at the thylakoid membrane


Thylakoids (green) inside a cyanobacterium ( Synechocystis )


TRP channel groups and families.


Figure 1. Light-activated TRPL channels in  Periplaneta americana  photoreceptors. A, a typical current through TRPL channels was evoked by a 4-s pulse of bright light (horizontal bar). B, a photoreceptor membrane voltage response to the light-induced activation of TRPL channels, data from the same cell are shown


TRPC5-mediated chemoresistance:   TRPC5 overexpression activates the transcription factor NFATC3 Ca 2+  signaling pathway, leading to p-gp overexpression. Moreover, the overexpressed p-gp expels chemotherapeutic drugs such as  doxorubicin  triggering chemoresistance.   Chemoresistant breast cancer cells overexpressing TRPC5 transfer channel units to chemo sensitive recipient cells via  extracellular vesicles  (EV), leading to the development of TRPC5-mediated chemoresistance in these cells. [ 49 ]


A turgid and flaccid cell


Mature squirting cucumber fruit


Tree roots penetrating rock


Open stomata on the left and closed stomata on the right


Mimosa pudica


Shaggy ink caps  bursting through asphalt due to high turgor pressure


Diagram of a pressure bomb


Type IV Secretion system


Scheme of a liposome formed by  phospholipids  in an  aqueous  solution


Sarfus  image of lipid vesicles


Electron micrograph of a cell containing a food vacuole (fv) and transport vacuole (tv) in a  malaria parasite


WALP-19 protein peptide of the following sequence of 19 amino acids: GWWLALALALALALALWWA. Tryptophan residues are shown in green while leucines and alanines are displayed in red and blue, respectively.


SNARE complex zoomed in to the zero ionic layer level on Pymol simulator


Amacrine cells. (Susanne E Hausselt, Thomas Euler , Peter B Detwiler, Winfried Denk.  License link )


A diagram of the retina of the eye.


A photograph of the retina of the human eye. (د.مصطفى الجزار,   License link )


A visual of the placement and use of the optic nerves. (OpenStax Textbook, Anatomy and Physiology,  License Link )


The conformation change of retinal, caused by light.


The three-layered network that carries photoreceptor information to the optic nerve. Photoreceptors are shown at the top, and the optic nerve is shown at the bottom.


Cells engineered to fluoresce under UV light.


Schematic of typical  Gram-positive cell wall  showing arrangement of  N-Acetylglucosamine  and  N-Acetylmuramic acid ;  Teichoic acids  not shown.


Schematic of typical  Gram-negative cell wall  showing arrangement of  N-Acetylglucosamine  and  N-Acetylmuramic acid  and the outer membrane containing  lipopolysaccharide .


Image of isolated adult  cardiac myocytes  taken using  confocal microscopy


Diagram A: Fluorescence-assisted cell sorting for negative selection.


Diagram B: Fluorescence-assisted cell sorting for positive selection.


The Hayflick limit deliberates that the average cell will divide around 50 times before reaching a stage known as senescence. As the cell divides, the telomeres on the end of a linear chromosome get shorter. The telomeres will eventually no longer be present on the chromosome. This end stage is the concept that links the deterioration of telomeres to aging.


Top : Primary mouse embryonic fibroblast cells (MEFs) before senescence. Spindle-shaped. Bottom : MEFs became senescent after passages. Cells grow larger, flatten shape and expressed senescence-associated  β-galactosidase  (SABG, blue areas), a marker of cellular senescence.


Chromatophores in the skin of a  squid


A  veiled chameleon ,  Chamaeleo calyptratus . Structural green and blue colours are generated by overlaying chromatophore types to reflect filtered light.


Leucophore layer composition


At the bottom a  mutant  zebrafish larva that fails to synthesise melanin in its melanophores, at the top a non-mutant, wildtype larva


The purple-striped dottyback,  Pseudochromis diadema , generates its  violet  stripe with an unusual type of chromatophore.


Fish and frog melanophores are cells that can change colour by dispersing or aggregating pigment-containing bodies.


A single  zebrafish  melanophore imaged by  time-lapse  photography during pigment aggregation


Zebrafish  chromatophores mediate  background adaptation  on exposure to dark (top) and light environments (bottom).


Cross-section  of a developing vertebrate  trunk  showing the dorsolateral (red) and ventromedial (blue) routes of chromatoblast migration


An infant  cuttlefish , using background adaptation to mimic the local environment


Coenocyte of  Sphaeroforma arctica


Botrydium , showing a coenocytic body


An eight-celled colony of  Pediastrum duplex


Models for studying collective cell migration   [ 10 ] Red arrows show the direction of migration for each tissue


Spectrum of collective cell migration   [ 25 ]


Alcohol dehydrogenase  immunoreactivity in a healthy cornea (top), in  Fuchs' dystrophy  and  keratoconic  cornea.  Diaminobenzidine  stains keratocytes in the cross-section of cornea. From  Mootha et al., 2009. [ 14 ]


1:posterior segment 2:ora serrata 3:ciliary muscle 4:ciliary zonules 5:Schlemm's canal 6:pupil 7:anterior chamber 8:cornea 9:iris 10:lens cortex 11:lens nucleus 12:ciliary process 13:conjunctiva 14:inferior oblique muscule 15:inferior rectus muscule 16:medial rectus muscle 17:retinal arteries and veins 18:optic disc 19:dura mater 20:central retinal artery 21:central retinal vein 22:optic nerve 23:vorticose vein 24:bulbar sheath 25:macula 26:fovea  27:sclera 28:choroid 29:superior rectus muscle 30:retina


Multiple exophers produced by a mechanosensory neuron in  C. elegans


1.The  insertion sequences  (yellow) on both the  F factor  plasmid and the chromosome have similar sequences, allowing the F factor to insert itself into the  genome  of the cell. This is called  homologous recombination  and creates an Hfr (high frequency of recombination) cell.   2.The Hfr cell forms sex pili a pilus and attaches to a recipient F- cell.   3.A nick in one strand of the Hfr cell’s chromosome is created.   4.DNA begins to be transferred from the Hfr cell to the recipient cell while the second strand of its chromosome is being replicated.   5.The pilus detaches from the recipient cell and retracts. The Hfr cell ideally wants to transfer its entire genome to the recipient cell. However, due to its large size and inability to keep in contact with the recipient cell, it is not able to do so.   6.The F- cell remains F- because the entire F factor sequence was not received. Since no homologous recombination occurred, the DNA that was transferred is degraded by enzymes. In very rare cases, the F factor will be completely transferred and the F- cell will become an Hfr cell.  [ 1 ]


Hülle cells from a single cleistothecium. Scale bar is 10 μm [ 1 ]


Cytopathology suspicious for  Hürthle cell neoplasm  ( Bethesda category  IV, rather than Hürthle cell hyperplasia), Pap stain. [ 5 ]


Rickettsia rickettsii  (stained red) within tick haemolymph cells.


Microscopic image of two ionocytes in a gill


Diagram of a lymph node.


Histological section  of a normal lymph node


Lymphocyte surrounded by red blood cells.


This is a 3D reconstruction of a neuropod cell utilizing a serial block face scanning electron microscopy (SBEM) data set in Imaris software. [ 1 ]  On the left side of the cell has microvilli extending into the gut lumen and the right side has a neuropod extending into the basal lamina propria. [ 1 ]


Culture of rat brain cells stained with antibody to MAP2 (green), Neurofilament NF-H (red) and DNA (blue). MAP2 is found in neuronal dendrites, while the neurofilament is found predominantly in axons. Antibodies and image courtesy of EnCor Biotechnology


Primordial Germ Cell Migration


Schematic model of somatic cell nuclear transfer. This technique has been used to create clones of an organism or in therapeutic medicine.


Schematic of CRISPR based gene editing technique


Rho Cascade - stress fiber formation


Three types of stress fibers: ventral stress fibers, transverse arcs, and dorsal stress fibers


Principle of transcriptional memory. A pulse of an inducer (priming) results in expression of target genes, which subsides upon withdrawal. During a window of no induction (window of memory), some genes maintain a poised but transcriptionally silent state that results in a stronger gene activation upon a second challenge.


Different types of extracellular signaling


Differences between autocrine and paracrine signaling


This image displays the different types of cell signaling


Transmembrane receptor working principle


The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2


A G Protein-coupled receptor within the plasma membrane


VEGF receptors are a type of enzyme-coupled receptors, specifically tyrosine kinase receptors


Key components of a signal transduction pathway ( MAPK/ERK pathway  shown)


Signal transduction pathways that lead to a cellular response


Notch -mediated juxtacrine signal between adjacent cells


A diagram of the proteins found in the active zone


The vesicle release machinery. [ 8 ]


The presynaptic active zone and the synaptic vesicle cycle


A diagram showing the change in membrane capacitance before (top) and after (middle and bottom) vesicle fusion.


General chemical structure of an  N -acyl homoserine lactone


Adenylyl cyclase catalyzes the conversion of  ATP  to  3',5'-cyclic AMP .


Structure of adenylyl cyclase


The human adhesion GPCR family .  Members are defined by their unusual hybrid structure in which a large extracellular region often containing known protein modules is coupled to a seven span transmembrane region via a GPCR-Autoproteolsis INducing  (GAIN)  domain.


GPCR-Autoproteolysis INducing  (GAIN)  domain , rat latrophilin  4DLQ  mediates autocatalytic cleavage of adhesion GPCRs


Activation of the PI3K-Akt Pathway by a Receptor Tyrosine Kinase


Structure of Phosphatidylinositol (3,4,5)-trisphosphate


Examples of feedback control in the PI3K-Akt Pathway


The substrates of Akt involved in promoting cell survival or blocking apoptosis


The effects of Akt activation on Cell Cycle progression


PI3K-Akt Pathway proteins involved in Cancer. Oncogenes (activation increases in cancer) are green and tumour suppressors (inactivated or lost in cancer) are red.


John Sulston  won the  Nobel Prize in Medicine  in 2002, for his pioneering research on apoptosis.


Control of the apoptotic mechanisms


Overview of signal transduction pathways


Different steps in apoptotic cell disassembly [ 61 ]


Long-term live cell imaging (12h) of multinucleated mouse pre-Adipocyte trying to undergo mitosis. Due to the excess of genetic material the cell fails to replicate and dies by apoptosis.


A section of mouse liver showing several apoptotic cells, indicated by arrows


A section of mouse liver  stained  to show cells undergoing apoptosis (orange)


Neonatal cardiomyocytes ultrastructure after anoxia-reoxygenation


Fig. 1: Activation of the  epidermal growth factor receptor  by autophosphorylation. Adapted from Pecorino (2008) [ 1 ]


Fig. 2: Regulation of Src-kinase by autophosphorylation. Adapted from Frame (2002) [ 2 ]


Shows Ca 2+  release from the  endoplasmic reticulum  through  phospholipase C (PLC)  pathway.


Phospholipase C cleaving PIP2 into IP3 and DAG


Comparison of smooth muscle and skeletal muscle contraction


The helix–loop–helix structure of the calcium-binding  EF hand  motif


This images shows conformational changes in calmodulin. On the left is calmodulin without calcium and on the right is calmodulin with calcium. Sites that bind target proteins are indicated by red stars.


Solution structure of Ca 2+ -calmodulin  C -terminal domain


Solution structure of Ca 2+ -calmodulin  N -terminal domain


Calmodulin bound to a peptide from MLC kinase ( PDB :  2LV6 )


Sorghum  plant contains temperature-responsive genes. These  genes  help the plant  adapt  in extreme weather conditions such as hot and dry  environments .


The seven-transmembrane α-helix structure of a G-protein-coupled receptor


E  =  extracellular space P  =  plasma membrane I  =  intracellular space


External reactions and internal reactions for signal transduction (click to enlarge)


Three conformation states of acetylcholine receptor (click to enlarge)


Sketch of an enzyme-linked receptor structure (structure of IGF-1R) (click to enlarge)


Flow charts of two strategies of structure-based drug design


Various types of cell junctions.  In this diagram, the interface between neighboring cells or the   basolateral membrane  is depicted as "sheets"; the space between these sheets being the extracellular environment and the location of adhesion protein interaction.


Immunofluorescence micrograph of three  cytotoxic T cells  (outer three) surrounding a cancer cell. Lytic granules (red) are secreted at the contact site, killing the target. Cytotoxic T cells are powerful agents of cellular immunity.


Labelled diagram of a cell undergoing apoptosis.


Alek Rapoport,  Anastasis I , 1996


HeLa cervical cancer cells


Artistic interpretation of the major elements in chemical synaptic transmission. An electrochemical wave called an  action potential  travels along the  axon  of a  neuron . When the action potential reaches the presynaptic terminal, it provokes the release of a synaptic vesicle, secreting its quanta of  neurotransmitter  molecules. The neurotransmitter binds to chemical receptor molecules located in the membrane of another neuron, the postsynaptic neuron, on the opposite side of the synaptic cleft.


Diagram of a chemical synaptic connection


Release of neurotransmitter occurs at the end of axonal branches.


Shoot apical meristems of Crassula ovata (left). Fourteen days later, leaves have developed (right).


Tunica-Corpus model of the apical meristem (growing tip). The epidermal (L1) and subepidermal (L2) layers form the outer layers called the tunica. The inner L3 layer is called the corpus. Cells in the L1 and L2 layers divide in a sideways fashion, which keeps these layers distinct, whereas the L3 layer divides in a more random fashion.


The sigmoidal shape of hemoglobin's oxygen-dissociation curve results from cooperative binding of oxygen to hemoglobin.


cAMP represented in three ways


Adenosine triphosphate


An antibody has  Fab  (fragment, antigen-binding) and Fc (fragment, crystallizable) regions. Fc receptors bind to the Fc region.


Fc receptors recognize  microbes  that have been bound by  antibodies . The interaction between the bound antibodies and the cell surface Fc receptor activates the immune cell to kill the microbe. This example shows the  phagocytosis  of an  opsonized  microbe.


Activation of mast cell degranulation by IgE interaction with FcεRI. 1 = antigen; 2 = IgE; 3 = FcεRI; 4 = preformed mediators (histamine, proteases, chemokines, heparin); 5 = granules; 6 – mast cell; 7 – newly formed mediators (prostaglandins, leukotrienes, thromboxanes, platelet-activating factor)


Crystal Structure of Fus3 MAP Kinase


Phosducin - transducin  beta-gamma complex. Beta and gamma subunits of G-protein are shown by blue and red, respectively.


Guanosine diphosphate


Guanosine triphosphate


Sequence relationship among the 18 human G α  proteins. [ 17 ]


Activation cycle of G-proteins (pink) by a G-protein-coupled receptor (GPCR, light blue) receiving a ligand (red). Ligand binding to GPCRs (2) induces a conformation change that facilitates the exchange of GDP for GTP on the α subunit of the heterotrimeric complex (3–4). Both GTP-bound Gα in the active form and the released Gβγ dimer can then go on to stimulate a number of downstream effectors (5). When the GTP on Gα is hydrolyzed to GDP (6) the original receptor is restored (1). [ 19 ]


GPCR-Autoproteolsis INducing  (GAIN)  domain , rat latrophilin  4DLQ  mediates autocatalytic cleavage of adhesion GPCRs


Connexin protein, modelled using pyMOL. pyMOL protein code taken from Protein Data Bank [ 19 ]


Calmodulin protein, modelled using pyMOL. pyMOL protein code taken from Protein Data Bank [ 21 ]


Structural formula of Amiodarone.


Structural formula of Tonabersat.


Glycine


(a): shows three agonists and one antagonist of the glycine receptor. (b): the fetal form of the receptor is made up of five α2 subunits, while the adult form is made up of both α1 and β subunits.


Figure 1.  Normal and Hedgehog mutant larvae.


Figure 2 . Production of the CiR transcriptional repressor when Hh is not bound to  Patched . In the diagram, "P" represents  phosphate .


Figure 3 . When Hh is bound to Patched (PTCH), Ci protein is able to act as a transcription factor in the nucleus.


Figure 4.  Interactions between  Wingless  and Hedgehog


Figure 5.  Overview of  Sonic hedgehog  signaling.


Suggested regulation pathway for Smo via Hedgehog and Ptch1


Figure 6.   Sonic hedgehog  specifies digit identity in mammalian development.


Figure 7 .  Phylogenetic  relationship of hedgehog ligands (based on Ingham and McMahon, 2001).


A generalized neuron containing heteroreceptors showing the release of different neurotransmitters than the heteroreceptor ligand.


Left: A hormone feedback loop in a female adult. (1)  follicle-stimulating hormone , (2)  luteinizing hormone , (3)  progesterone , (4)  estradiol . Right:  auxin  transport from leaves to roots in  Arabidopsis thaliana


Different types of hormones are secreted in the human body, with different biological roles and functions.


The left diagram shows a steroid (lipid) hormone (1) entering a cell and (2) binding to a receptor protein in the nucleus, causing (3) mRNA synthesis which is the first step of protein synthesis. The right side shows protein hormones (1) binding with receptors which (2) begins a transduction pathway. The transduction pathway ends (3) with transcription factors being activated in the nucleus, and protein synthesis beginning. In both diagrams, a is the hormone, b is the cell membrane, c is the cytoplasm, and d is the nucleus.


Blood glucose levels are maintained at a constant level in the body by a negative feedback mechanism. When the blood glucose level is too high, the pancreas secretes insulin and when the level is too low, the pancreas then secretes glucagon. The flat line shown represents the homeostatic set point. The sinusoidal line represents the blood glucose level.


This is a diagram that represents and describer what hormones are and their activity in the bloodstream. Hormones flow in and out of the bloodstream and are able to bind to Target cells to activate the role of the hormone. This is with the help of the bloodstream flow and the secreting cell. Hormones regulate: metabolism, growth and development, tissue function, sleep, reproduction, etc. This diagram also lists the important hormones in a human body.


The  T-cell receptor complex  with TCR-α and TCR-β chains,  CD3  and ζ-chain accessory molecules. ITAMs are represented in blue on the tails of the CD3 subunits.


Notch -mediated juxtacrine signal between adjacent cells


Kainic acid


Glutamic acid


Known KAR Roles in Neurons


Human hypothalamus (shown in red)


GNRH1 structure


Figure 28 03 01


Myoglobin  (blue) with its ligand  heme  (orange) bound. Based on  PDB :  1MBO


Two agonists with similar binding affinity


Two ligands with different receptor binding affinity.


Function of TAM.


Key components of the MAPK/ERK pathway. "P" represents   phosphate , which communicates the signal. Top, epidermal growth factor (EGF) binds to the EGF receptor (EGFR) in the cell membrane, starting the cascade of signals. Further downstream, phosphate signal activates MAPK (also known as ERK). Bottom, signal enters the cell nucleus and causes transcription of DNA, which is then expressed as protein.


MAP Kinase Pathways.


Schematic of mitogen input integrated into the cell cycle


EGF-Stimulated, Frequency-Modulated ERK Activity Pulses


The figure shows the interaction and cooperation of MEK, DUSP5 and DUSP6/MKP-3 within the cytoplasmic region and the nucleus. RAF activates MEK. Activated MEK phoshorylates ERK which can now be transported across the cell membrane by a transporter. Dephosphorylated ERK cannot leave the nucleus.


When activated MAPK binds to MKB this causes a conformational change of the DUSP region which activates MKP and activated MKP dephosphorylates MAPK thereby inactivating it.


Some  biological machines


Mechanically gated channel


Cartilage experience tension, compression and shear forces in vivo


Chondrocyte surface mechano-receptors include CD44, annexin V and integrins. Chondrocyte extracellular matrix components include collagens, proteoglycans (which consist of aggrecan and hyaluronan), fibronectin and COMP.


Release of cytochrome c through MAC [ 1 ]


An overview of tools discussed that are used for the rule-based specification and particle-based evaluation (spatial or non-spatial) of multi-state biomolecules.


Principles of particle-based modeling. In particle-based modeling, each particle is tracked individually through the simulation. At any point, a particle only "sees" the rules that apply to it. This figure follows two molecular particles (one of type A in red, one of type B in blue) through three steps in a hypothetical simulation following a simple set of rules (given on the right). At each step, the rules that potentially apply to the particle under consideration are highlighted in that particle's colour.


Screenshot from an MCell simulation of  calcium signaling  within the spine. Although other types of calcium-regulated molecules were included in the simulations, only CaMKII molecules are visualized. They are shown in red when bound to calmodulin and in black when unbound. The simulation compartment is a reconstruction of a  dendritic spine . [ 54 ]  The area of the  postsynaptic density  is shown in red, the spine head and neck in gray, and the parent dendrite in yellow. The figure was generated by visualizing the simulation results in  Blender .


Alpha5 nicotinic acetylcholine 3D structure


Conditioned place preference experiment designed on Biorender.com


Acetylcholine


Nicotine


Nicotinic receptor structure


Stylized depiction of an activated NMDAR. Glutamate is in the glutamate-binding site and glycine is in the glycine-binding site. The  allosteric site , which modulates receptor function when bound to a ligand, is not occupied. NMDARs require the binding of two molecules of  glutamate  or  aspartate  and two of  glycine [ 1 ] [ 2 ]


Cartoon representation of the human NMDA receptor. Each subunit is individually rainbow colored.


Figure 1:  NR1/NR2 NMDA receptor


Figure 2:  Transmembrane region of NR1 (left) and NR2B (right) subunits of NMDA receptor


NR2 subunit in vertebrates (left) and invertebrates (right). Ryan et al., 2008


The timecourse of GluN2B-GluN2A switch in human cerebellum. Bar-Shira et al., 2015  [ 44 ]


L - Glutamic acid  (glutamate), the major endogenous agonist of the main site of the NMDAR


Glycine , the major endogenous agonist of the glycine co-agonist site of the NMDAR


Figure 6:  Chemical structure of neramexane, second generation memantine derivative


N -Methyl- D -aspartic acid  (NMDA), a synthetic partial agonist of the main site of the NMDAR


Ketamine , a synthetic general anesthetic and one of the best-known NMDAR antagonists


Figure 7:  Nitroglycerin donate ONO 2  group that leads to second generation memantine analog, nitromemantine


Figure 4:  The chemical structures of MK-801, phencyclidine and ketamine, high affinity uncompetitive NMDA receptor antagonists


Figure 5:  Chemical structures of memantine (right) and amantadine (left)


Figure 8:  Structure activity relationship (SAR) of amantadine and related compounds


O -GlcNAc is a post-translational modification found on serine and threonine residues defined by a β-glycosidic bond between the side-chain hydroxyl and  N -acetylglucosamine. GlcNAc moiety shown in red.


Serine in a polypeptide with no modifications (top) and with an  O -GlcNAc modification (bottom). ( PDB : 4GYW)


GalT radiolabeling of cellular proteins with UDP-[ 3 H]galactose followed by β-elimination yielded Galβ1-4GlcNAcitol, suggesting that the substrate for GalT was  O -GlcNAc. Radiolabeled [ 3 H]galactose shown in red.


O -GlcNAcylation of serine and threonine residues is dynamically controlled by OGT and OGA.


Left : Model of full-length ncOGT in complex with CKII peptide substrate and UDP. [ 16 ]  Colors indicate TPR domain (gray), N-terminal region of catalytic domain (light pink), intervening domain (light green), C-terminal region of catalytic domain (light blue), CKII peptide substrate (green), and UDP (cyan).  Right : Structure of human OGA D175N dimer in complex with  O -GlcNAcylated TAB1 peptide substrate. Monomers shown in blue-white/light yellow with respective peptide substrates in blue/yellow. (PDB: 5VVU)


Chemoenzymatic labeling for the detection of  O -GlcNAc. GalT Y289L transfers GalNAz to  O -GlcNAc, providing a handle for click chemistry. Various probes can be conjugated via azide-alkyne cycloaddition. Attachment of a PEG5K mass tag allows for visualization of  O -GlcNAc stoichiometry.


FRET biosensor for  O -GlcNAc. Under high  O -GlcNAc conditions, GafD will bind the  O -GlcNAc group on the CKII peptide substrate, bringing CFP and YFP into proximity for FRET. Various localization sequences can be fused to localize the sensor to various cellular compartments, e.g., nucleus, cytoplasm, and plasma membrane.


Structure of IsoTaG probe. Probe consists of a biotin affinity tag (red), a linker (black), an acid-cleavable silane (blue), an isotope recoding motif (green), and an alkyne (purple).


Site-directed mutagenesis for manipulating  O -GlcNAc. S/T-to-A mutagenesis prevents  O -GlcNAc modification at that residue. S/T-to-C mutagenesis allows for generation of the  S -GlcNAc modification, a structural analogue of  O -GlcNAc that is not readily hydrolyzed by OGA.


MK-8719, an OGA inhibitor, suppresses tau aggregation by elevating  O -GlcNAc levels on tau. Post-translational modifications are indicated as G ( O -GlcNAc), P (phosphorylation), Ub (ubiquitination), Ac (acetylation), and N (nitration). Adapted from. [ 105 ]


Figure 2. Crystal structure of the zebrafish P2X 4  receptor (deltaP2X4-B) channel as viewed from the side (left), extracellular (top right), and intracellular (bottom right) perspectives( PDB :  3I5D )


PIP2 cleavage to IP3 and DAG


Phospholipase C-delta isoform 1. Blue plane shows hydrocarbon boundary of the  lipid bilayer


Phospholipase cleavage sites. An enzyme that displays both PLA 1  and PLA 2  activities is called a  phospholipase B .


Serine  in an amino acid chain, before and after phosphorylation.


General PI(4,5)P2 cycle


PIAS and the  JAK-STAT pathway . Upon stimulation by  IL-6 ,  PIAS3  can inhibit  transcription activation  by activated  STAT3 .


PHD zinc finger domain  of SIZ1. SIZ1 is a PIAS protein homologue found in yeast.


The domains (SAP, RLD, AD, S/T) and motifs (PINIT, SIM) found in most protein inhibitors of activated STAT (PIAS)


p53 binding domain of PIAS-1.


Model of a phosphorylated  serine  residue


Serine in an amino acid chain, before and after phosphorylation.


The AXL receptor tyrosine kinase, showing the symmetry of the dimerized receptors


Example of posttranslational modification detected on a 2D gel (spot boundaries delimited by analysis software, identification by mass spectrometry, P46462 is the protein ID in Expasy)


Pseudomonas aeruginosa


Exogenously applied ATP stimulates the closure of the  Venus flytrap [ 5 ]


Homology modeling  of the  P2RX2  receptor in the open channel state