Lipids and Membranes PDF

[email protected] Dr Christina Warboys Lipids and Membranes BSc Year 1 & Gateway | 2024-202 5| Biology of Cells – cell structure and function Learning outcomes for this lecture At the end of this topic students should be able to: Describ...

[email protected] Dr Christina Warboys Lipids and Membranes BSc Year 1 & Gateway | 2024-202 5| Biology of Cells – cell structure and function Learning outcomes for this lecture At the end of this topic students should be able to: Describe the properties of the lipid bilayer and the general structure of cell membranes. Explain how membrane lipids, proteins and carbohydrates are associated with the lipid bilayer. Outline how membranes are specialised to allow cargo to cross them: lipid rafts, caveoli and vesicles. Briefly explain some of the mechanisms pathogens have developed to overcome or breakdown the plasma membrane barrier Why is this important Pathogens must cross cell membranes to infect a host Drugs must cross cell membranes to exert effects Dysfunction of membrane components or processes is associated with some pathologies Universal features of cells The natural world has remarkable variety but constancy in fundamental mechanisms All cells are enclosed in a cell membrane  The membrane surrounding eukaryotic cells is known as the PLASMA MEMBRANE  Sub-cellular organelles are also surrounded by membranes. Functions of cell membranes The semi-permeable membrane allows cells to: be physically separated from the external environment. form a barrier against pathogens take in nutrients, minerals, ions, water etc. excrete waste products from the cell. receive and act on signals from outside & send signals to other cells (more on this in Unit 2) Building blocks of the plasma membrane All membranes have the same BILAYER structure and are composed of: Lipids - responsible for forming the basic structure that seals each cell from its external environment.  made up from phospholipids and cholesterol Proteins – responsible for communication with the external environment:  comprising receptors, channels and pumps Carbohydrates - present in small amounts on the outside surface of the cell, either as glycoproteins or glycolipids Membrane Lipids All lipids in cell membranes are amphipathic/amphiphilic because they water contain domains that are Hydrophillic (polar) and Surface film Hyrdophobic (non-polar) Spontaneously organise to form a bilayer Aqueous (Extracellular) non-polar Hydrophilic heads interact with the aqueous phase environment Hydrophobic tails crowd inward away from Aqueous (Intracellular) the aqueous environment. Lipid Bilayer Phospholipid structure Phospholipid structure The most abundant membrane lipids are phospholipids The main phospholipids are phosphoglycerides which have: A glycerol backbone which links Phosphate group in the polar head with Two long-chain fatty acid tails PHOSPHATIDLYCHOLINE Asymmetry of membrane lipids Plasma membranes contain 4 major phospholipids Phosphatidylcholine Phosphatidylethanolamine Phosphatidylserine Sphingomyelin Distributed asymmetrically across the membrane Outer membrane phosphatidylcholine & Sphingomyelin Inner membrane phosphatidylethanolamine & phosphatidylserine & Phosphatidylinositol (an important cell signallng molecule) PS and PI have negatively charged head groups so give a net negative charge to cytosolic side of membrane Fluid mosaic model of the plasma membrane Cell membranes are dynamic - lipids and protein are able to diffuse freely (lateral movement) Fluidity must be tightly controlled to maintain membrane function Fluidity depends on temperature Phase transition at lower temperatures Fluidity depends on composition of fatty acid tails hydrocarbon chain length presence of double bonds  Flexible non-polar side chain Cholesterol Modulates properties of lipid bilayers Hydroxyl groups associate with polar head groups of adjacent phospholipids Rigid steroid rings Provides structure and rigidity Polar hydroxyl group Also influences membrane fluidity.  At cold temperatures cholesterol prevents phospholipids packing together and maintains fluidity But…..not all lipids diffuse freely in the membrane…… Membrane specialisations - Lipid rafts Some lipids are restricted within specialised membrane microdomains (lipid rafts), enriched in Cholesterol Sphingomyelin Glycolipids Within lipid rafts, fatty acid tails are more saturated allowing tighter packing of phospholipids Rafts can move laterally within the membrane Associated with specific membrane proteins Enriched in GPI-anchored proteins Allows compartmentalisation of cellular processes and is important for Cell signalling Endocytosis Permeability of the lipid bilayer In the absence of proteins, the lipid bilayer is largely impermeable to many essential substances large, uncharged H2O and other polar molecules small, uncharged hydrophobic (glucose etc.) ions polar molecules molecules Lipid Bilayer Requires the presence of pumps, channels and transporters Functions of membrane proteins Transport specific molecules Provide channels for ion passage Receptors for external cues (chemical, physical) Structural links to other cells Enzyme activity  Protein associations with the lipid bilayer Integral membrane Oligosaccharide link (transmembrane) proteins extracellular cytosol single pass multipass anchored by covalent link to non covalent α-helix protein-protein interactions lipid anchor Monotopic membrane proteins Peripheral membrane proteins Membrane-spanning portions usually α-helices of 20-25 hydrophobic amino acids Membrane carbohydrates proteoglycan Up to 10% of membrane mass is carbohydrate. Carbohydrate is found ONLY on the exterior side of the membrane. glycoprotein  Most proteins and about 10% of lipid molecules (glycolipids) exposed at the cell surface have glycolipid sugar residues attached. There are two types of protein-carbohydrate molecules: cytosol  Glycoproteins are mostly protein, with some sugars attached. proteins  Proteoglycans have very long, branching carbohydrate chains (90% carbohydrate). polysaccharide chains Glycocalyx Literally means sugar coat (glyky=sweet, calyx=husk) Endothelial cells in blood vessels Bacteria Modulates leukocyte-endothelial interactions Prevents thrombus formation Bound to the cell wall (capsule) Adhesion to surfaces Regulates vascular permeability Prevents recognition by immune Contains mechanosensors and receptors cells Cell identification – self/non-self recognition Transport across cell membranes Endocytosis The mechanism by which cells internalise substances from the external environment or remodel membrane composition Part of the plasma membrane buds inwards to make an internal bubble which then pinches off internalising cargo. Important for: Nutrient uptake Membrane protein recycling Synaptic vesicle recycling Cell signalling Entry of pathogens Phagocytosis Can be receptor-mediated Clathrin-mediated endocytosis (CME) The major endocytic pathway in mammalian cells Dependent on binding of clathrin to internal membrane (via adapter proteins) 1) Macromolecules bind to specific cell surface receptors e.g. Low-density lipoprotein binds to LDL receptor 2) Receptors cluster and recruit clathrin which builds a coat around the membrane forming a clathrin-coated pit 3) An actin network forms around clathrin and helps bend membrane inward 4) The neck of mature pits is cleaved from the membrane by dynamin to form small clathrin-coated vesicles containing receptors and bound cargo 5) Vesicles fuse with early endosomes for sorting of cargo 6) Clathrin is recycled back to membrane https://doi.org/10.1242/jcs.39 Caveolae-mediated endocytosis Caveloae are a type of lipid raft Flask shaped invaginations of the plasma membrane Enriched in caveolin proteins that cluster on the inner membrane Can bud off from the membrane forming an endocytic vesicle Budding is regulated by kinases and phosphatases Requires dynamin for scission of vesicle https://doi.org/10.2147/IJN.S274289 Independent of clathrin Extracellular vesicles Extracellular vesicles are nano-sized lipid bilayer delimited particles that are released from almost all cells Exosomes (released by exocytosis) Microvesicles (released by outward budding and shedding) Apoptotic bodies (released from dying cells) Found in plasma, urine, breast milk, saliva Contain bioactive molecules e.g. lipid, protein, metabolites, RNA, DNA Composition will depend on physiological or pathological state Important role in cell-to-cell communication Exocytosis and neurotransmitter release Exocytosis is the fusion of secretory vesicles with the plasma membrane and bulk release of cargo into the extracellular space Active transport process Neurotransmission is an example of exocytosis A synaptic vesicle containing neurotransmitter releases its contents into the synaptic cleft Vesicles dock at and fuse with the membrane Occurs in response to increased intracellular calcium Rapid release (