Cellular Physiology: Biomembranes

• The lecture is about cellular and molecular physiology, specifically focusing on biomembranes.

Biomembrane Definition

• Biomembranes are barriers which prevent cell contents from being leaked out.
• The cell membrane affects form and function.
• Proteins are anchored to the membrane.
• Modifying activity of membrane proteins exists.
• Cell membranes translate signals to the cytoplasm.
• Selective barriers are their main objective.
• Living cells use auto-reproduction of molecules, biomembranes are the containers.
• Biomembranes are composed of a lipid leaflet.

Fluid Mosaic Model

• The Fluid mosaic model thickness is 3nm.
• In the Fluid mosaic model, integral membrane proteins and lipid-anchored proteins are found in the cytosol.
• In the Fluid mosaic model, lipid-anchored proteins and peripheral membrane proteins are found in the exoplasm.
• Hydrophilic phospholipid head groups, and phospholipid bilayers compose membranes.
• Hydrophilic fatty acyl side chains found in phospholipid bilayers.

Structural Organization

• Organelles are surrounded by one or more biomembranes.
• Each type of organelle has a unique set of proteins.
• Some proteins are embedded in the membranes, others bathe in the cell's lumen.
• Reactions in eukaryotes are limited by the diffusion of small molecules, inside organelles.
• A cell's plasma membrane defines the exterior.
• It controls molecule displacement between the cytosol and the extracellular medium.
• Organites and vesicles execute particular functions.
• Cytoskeleton fibres offer structual support to the cell and its compartments.
• Internal membranes of organites and vesicles have a larger membrane, but it is less extensive than the cytoskeleton.

Eukaryote Membranes and Components

• Eukaryote membranes are dynamic.
• Plasma membrane is 700µm².
• Internal membranes are 7000µm².
• The Cytoskeleton is 94,000µm².

Membrane Bilayers and Lipid Structures

• Membrane bilayers have an exterior that faces the cell exterior and the cytosol.
• Membrane bilayers possess polar head groups that are hydrophilic.
• Membrane bilayers possess also hydrophobic tails in the middle.

Structure in Bilayer Membranes

• Erythrocyte membranes marked with osmium tetroxide show two polar layers corresponding to the phospholipid bilayer.
• Polar groups of the lipid bilayer are oriented towards the exterior for hydrophilic protection.
• Van der Waals interactions between fatty acid tails are the source of bilayer assembly.
• The lipid bilayer prevents diffusion of molecules in water.
• Membrane proteins regulate transport of specific molecules.
• Interactions are maintained through hydrophobic forces.

Lipid Composition

• Biomembranes consist of three lipid classes, phosphoglycerides, sphingolipids, and amphipathic lipids.
• Phosphoglycerides are glycerol3-phosphate derivatives and possess a phosphate headgroup.
• Phosphoglycerides include phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, and phosphatidylinositol.

Sphingolipids

• Sphingolipids include sphingomyelines and glucosylcerebroside.

Table of Lipid Components

• The table shows the composition of biomembranes in mol%.
• The plasma membrane of human erythrocytes comprises 21% PC, 29% PE+PS, 21% SM, and 26% cholesterol.
• Myelin membrane in human neurons comprises 16% PC, 37% PE+PS, 13% SM, and 34% cholesterol.
• Plasma membrane of E. Coli comprises 0% PC, 85% PE+PS, 0% SM, and 0% cholesterol.
• The PC = phosphatidylcholine.
• PE = phosphatidylethanolamine.
• PS = phosphatidylserine.
• SM = sphingomyelin.

Molecule Displacement

• Molecules diffuse laterally.
• Flipping sides rarely occurs.
• Lateral movement in membranes of proteins and lipids.
• Temperature causes lipid shifts around their axes.
• Fatty acid chains reside in the membrane interior.
• Proteins separate the phosopholipids.
• Lipids are linked to intrinsic membrane proteins.
• Lipid movements in leaflets are unidirectional, or bidirectional.
• FRAP (fluorescence recovery after photobleaching) quantify protein and lipid displacement.

Fluorescence Recovery After Photobleaching

• Fluorescence before bleaching is higher than fluorescence than after a bleaching process.
• Some molecules end up immobile (50%), whilst others are mobile (50%)

Flipping and Replacements

• Flip-flop is a rare process.
• Phospholipids diffuse quickly along the plane of the membrane.
• Replacement occurs at a rate of 10^-8 seconds.
• ATP hydrolysis is required since lipids are transported against concentration gradients.
• Flippases of type P4 transport lipids from the external layer of the membrane into the internal/cytoplasmic layer.
• Floppases transport lipids from the internal layer to the external layer.

Membrane Properties

• Every cell contains multiple kinds of membranes.
• Organs are different, so membranes specialize to particular functions.
• Phosphoglycerides, Sphingolipids are found in basolateral and apical membranes.
• Apical intestinal membranes have more sphingolipids, and the same amount of other structures than basolateral.

Fluidity

• Fluidity depends on lipid composition, tails, and temperature.
• Inserts itself between the phospholipids.
• Cholesterol maintains membrane fluidity by limiting the head's displacement.
• Lipid composition and thickness are related.
• Thicker in Sphingomyelin bilayers.
• Cholesterol increases the thickeness, not in the SM bilayer.

Membrane Lipids

• Size and tails relate to curvature.
• Lipids form bilayers that are flat in appearance.
• PC have planar arrangements in membranes.
• Conical lipids present concave layers.
• PE appear in a curved membrane.
• A bilayer rich in PC has a natural bend on the non-cytosolic layer.
• A bilayer rich in PE has a natural bend on the cytosolic layer.

Membrane Proteins

• Membrane proteins interact with the bilayer either via its interior or surface.
• Membrane protein types and densities vary among cell types.
• Relations occur between structure and functions, and it varies in the extracellular matrix, exterior, and cytosol.

Interactions

• Integral proteins are embedded in the membrane.
• Lipid-anchored have the attached lipid anchored in the membrane.
• Peripheral proteins are not directly embedded.
• Integral proteins have parts that can exist in the extracellular, cytosolic, and membrane layers.
• a helices: 20-25 hydrophobic acids, interact with lipids, held by van der waals forces.

Lipid Anchorage

• Linked to one or more lipid molecules.
• Hydrophobic chains are embedded in the leaflet.
• These chains attach to proteins within the cell membrane.

Peripheral Proteins

• Peripheral proteins exist at the cystolic and exoplasmic faces.
• They do not interact with the central bilayer.

Protein Orientation

• PAL are oriented in membrane axes. The membrane is asymmetrical.
• Transmembrane proteins have chains of sugars/glycans.
• Chains are attached to Serine, Threonine, and Asparagine.
• These all result in different properties for each membrane face.

Membrane Difference example blood

• Erythrocytes have oligosaccharides on the surface.
• These attach to glycolipids.
• Everybody has the enzymes that creates the O antigen.
• A: the isoform of glycocyltransferase that adds to the O antigen is N-acetylgalactosamine.
• B: the isoform of transferase adds galactose.
• AB: have a transferease and also an antigen.
• O: has neither an enzyme nor an antigen.

ABO Blood Groups

• O: anti-A and anti-B
• Can recieve:
  • A: anti-B, A and O
  • B: anti-A, B and O
  • AB: None, All
  • O: Anti-A and Anti-B, O

Membrane Roles

• The Plasma Membrane serves as a barrier for harmful materials.
• It is permeable to water.
• Each organ has a set of proteins for functions and endosomes absorb macromolecules.
• Pexoxisomes degrade lipids and toxic molecules.
• The ER creates lipids and membrane proteins.
• The golgi matures/sorts secreted proteins.
• Mitochondria are a source of ATP production.
• Lysosomes are enzymes used to degenerate components.

Tay Sachs Disease

• Named after Warren Tay and Bernard Sachs.
• Tay described retina issue in 1881.
• Sachs worked with cell modification, observed mainly in Jewish pop.
• It is linked to consanguineous marriages.