W3- Plasma Membrane.pptx

Biological membranes: Structure and Function of the Plasma Membrane Dr Anissa Chikh 29-09-2023 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of t...

Biological membranes: Structure and Function of the Plasma Membrane Dr Anissa Chikh 29-09-2023 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of the main functions of the Plasma Membrane cell recognition receptors and cell communication transport 4) To appreciate the clinical significance of Plasma Membrane components Further reading: Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (8th/9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). 2 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of the main functions of the Plasma Membrane cell recognition receptors and cell communication transport 4) To appreciate the Clinical significance of the Plasma Membrane components Suggested further reading: Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). 3 Biological membranes Lysosome Mitochondrial inner and outer Plasma membrane Golgi Endoplasmic reticulum (ER) Nuclear envelope 4 Cells are full of different membrane compartments 1µm Nuclear envelope Nucleus Golgi stacks ER PM Mitochondrial Lysosome Endomembrane system Electron micrograph: Human endothelial cell, Courtesy of Dr Matthew J Hannah, Public health England. 5 Common features underlie the diversity of biological membranes Nuclear envelope Nucleus • membranes are sheet like structures a few molecules thick that form closed boundaries Golgi stacks Mitochondrial • Membranes consist of lipids, proteins and carbohydrates linked to lipids or proteins • Membranes are non-covalent assemblies • Membranes are fluid structures ER Lysosome • Most membranes are asymmetric in composition • Most membranes are electrically polarised PM 6 Introduction The plasma membrane • Performs functions essential for life • Protective barrier, 7.5-10 nm, thick that separates living cells from the surroundings • Cell composition: control of the movement of nutrients, ions, proteins etc in and out of cell • Cell identity and function • Cell communication (signal transduction) 7 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of the main functions of the Plasma Membrane cell recognition receptors and cell communication transport 4) To appreciate the Clinical significance of the Plasma Membrane components Suggested further reading: Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). 8 Structure of the Plasma Membrane Composition Membrane Lipids Membrane Proteins Membrane Carbohydrates Fluid mosaic model 9 1. Structure of the plasma Membrane Lipid composition membrane Fatty acid residue • Phospholipids (most abundant) • Phosphoglycerates (glycerol backbone) • 2 fatty acid chains • Phosphorylated alcohol: choline, ethanolamine, Phosphatidylchol ine serine, inositol • Sphingomyelin (sphingosine backbone) Sphingoglycolipi d Sugar (Glucose/Galactose) • Glycolipids • Glycerol or sphingosine backbone (glyceroglycolipids and sphingolipids) • Fatty acid residue Sphingosine backbone Contain a carbohydrate (sugar) component Hydrophobic tail 10 1. Structure of the plasma Membrane Lipid composition membrane • Cholesterol • May constitute up to 50% of the lipid membrane • Smaller molecule and less amphipathic cholester ol hydrophobic Polar 11 1. Structure of the plasma membrane Membrane Lipids : bilayer formation Amphipathic molecules Na-palmitate (soap) Micelle • Spontaneously form bilayers in aqueous solutions. • Tend to be extensive in size. • Cooperative structures (electrostatic forces,hydrogen bonds) • Two molecules-thick, forms closed boundaries • Self sealing 12 1. Structure of the plasma membrane Membrane Lipids : bilayer formation Amphipathic molecules Na-palmitate (soap) Micelle liposomes 13 1. Structure of the plasma membrane Membrane Lipids : Lipid asymmetry SM Sphingomyelin PC Phosphatidylcholine PS Phosphatidylserine PE Phosphatidylethanolami ne PI Phosphatidylinositol Cl Cholesterol Membrane asymmetry Flippase 14 1. Structure of the plasma Membrane composition: membrane Proteins Integral Membrane Proteins • • • • Single or multi-pass Partially embedded (Prostaglandin H2 synthase) Non-covalent bonds Transmembrane helix Prostaglandin H2 synthase Biochemistry 7th Ed. L. Stryer, Fig. 12.23, Chp12 15 1. Structure of the plasma Membrane composition: membrane Proteins Integral Membrane Proteins • • • • Single or multi-pass Partially embedded (Prostaglandin H2 synthase) Non-covalent bonds Transmembrane helix Peripheral Membrane Proteins • • • Located outside or inside the cell Non-covalent bonds Interacts with integral proteins or polar head groups Lipid-anchored Membrane Proteins • • Covalent bonds to a lipid molecule Example of GPI (glycerophosphoinositol) e.g Alkaline phosphatase, Glypican 16 1. Structure of the plasma membrane Membrane composition: Carbohydrates • Carbohydrates associated with both membrane lipids (Glycolipids) and proteins (Glycoproteins) • Carbohydrates are exclusively presented on the extracellular side of the plasma membrane (asymmetry) 17 1. Structure of the plasma membrane Fluid Mosaic Model (SJ Singer and GL Nicolson, 1972) Fluid mosaic model Individual phospholipids and proteins can move side-to-side within the layer Pattern produced by the lipids, scattered protein and carbohydrates 18 1. Structure of the plasma membrane Fluidity Fluid mosaic model 1-2µm2/s ~once per month Flippases: catalyse the rapid flip flop of phospholipids 19 19 1. Structure of the plasma membrane Fluid mosaic Fluidity model Fatty acid composition and saturation influences fluidity Saturated hydrocarbon tails Lipids are more viscous Unsaturated hydrocarbon tails Lipids are more Fluid 20 1. Structure of the plasma Fluid mosaic model membrane Fluidity Cholesterol modulates membrane fluidity hydrophobic Polar • At low temperatures cholesterol prevents phospholipid tight packing and maintains fluidity (increases membrane fluidity at low temperature) • At warm temperatures cholesterol restricts phospholipid diffusion (prevents membranes becoming to fluid at high temperature) 21 1. Structure of the plasma Fluid mosaic model membrane Fluidity Cholesterol has many other essential roles hydrophobic Polar • sterols regulate O2 entry into eukaryotic cells and organelles • sterols act as O2 sensors across all eukaryotic life forms • sterols serve as a primitive cellular defence against O2 (including reactive oxygen species). 22 Sterols may have evolved in eukaryotes as an adaptive response to the rise of terrestrial O2 1. Structure of the plasma membrane Fluid mosaic model Mosaic 23 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of the main functions of the Plasma Membrane cell recognition receptors and cell communication transport 4) To appreciate the Clinical significance of the Plasma Membrane components Suggested further reading: Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). 24 Functions of the plasma membrane Lipids: Establish semi-permeable barrier between external and internal aqueous environment Provide environment in which proteins can dissolve and function. Cell- Cell Recognition (Surface Identity Markers) Transport Enzyme Receptor Adhesion Attachment Proteins: Cell- Cell Recognition (Identity) Signal Transduction (Receptor) Transport Enzymatic activity Attachment (cytoskeleton or extracellular matrix) Intercellular junctions (Adhesion) Identity 25 2. Function of the plasma membrane Cell-Cell Recognition (Surface Identity Marker) • Determine blood type : A, B, O or AB • Play a key role in cell-cell recognition • Basis for rejection of foreign cells by immune system Blood cell antigens: Glycolipids 26 2. Function of the plasma membrane Signal Transduction (Cell Surface receptors) Hormones or Neurotransmitters Induce cell response Activate cellular pathways Cholera toxin : over-activation of Gs protein Pertussis toxin : inhibits Gs protein cAMP cAMP Diarrhoea Whooping cough 2. Function of the plasma membrane Transport simple diffusion facilitated diffusion active transport 28 2. Function of the plasma membrane Transport Passive transport : Simple Diffusion Facilitated Diffusion Osmosis Small molecules (O2, CO2, water) and hydrophobic molecules Ions, hydrophilic molecules, and large molecules (proteins) • NO ENERGY needed – chemical potential-driven • Move from HIGH to LOW concentration towards EQUILIBRIUM 29 2. Function of the plasma membrane Transpor Simple Diffusion Facilitated Diffusion Osmosis t Carrier Mediated facilitated diffusion Solute concentration Passive transport : simple diffusion Time • Passive transport aided by proteins • Massively speeds up passive movement of molecules 30 2. Function of the plasma membrane Transpor Passive transport : Simple Diffusion t Channel proteins – eg: Aquaporins – eg: Ion channels Facilitated Diffusion Osmosis Diffusion With help (protein transporter/carrier) • Carrier proteins Membrane becomes semi-permeable with protein channels/carriers 31 2. Function of the plasma membrane Transpor Passive transport : t Glucose transporter Simple Diffusion Facilitated Diffusion Osmosis More than one transporter for the same 32 molecule 2. Function of the plasma membrane Transpor Passive transport : t Simple Diffusion Facilitated Diffusion Osmosis Process by which water diffuses across a membrane from the region of lower solute concentration to the region of higher solute Concentration to balance the solute concentrations 33 2. Function of the plasma membrane Transpor Passive transport : t Animal cells (no cell wall) Simple Diffusion Facilitated Diffusion Osmosis Hypotonic Isotonic Hypertonic Hypotonic solution : Solute concentration outside cell < inside the cell = Cell gains water Isotonic solution : Solute concentration outside cell = inside cell = no net water movement Hypertonic solution : Solute concentration outside cell > inside cell = Cell loses water 34 Cell survival depends on balancing water uptake 2. Function of the plasma membrane Transport Active Transport • Active transport : ENERGY input needed (ATP) • Moves substances from LOW to HIGH concentration (against concentration gradient) • Allows cells to maintain concentration gradients that differ from their surroundings ATP Protein conformational changes 35 2. Function of the plasma membrane Transport Active Transport Na+-K+-ATPase (antiporter) Creates Na+ gradient that can be used by secondary transporter 36 2. Function of the plasma membrane Transport Active Transport Na+ enters with Na+-Glucose symporter (SLAC5A1/2) and is pumped out by Na+-K+-ATPase to maintain the Na+ concentration gradient 37 2. Function of the plasma membrane Transport Active Transport: Gut Glucose Transport 38 Learning objectives: 1) To appreciate the diversity and common features of biological membranes 2) To understand the key structural components that makeup the Plasma Membrane 3) To understand some of the main functions of the Plasma Membrane cell recognition receptors and cell communication transport 4) To appreciate the Clinical significance of the Plasma Membrane components Suggested further reading: Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). 39 2. Function of the plasma membrane Transport Active Transport: Clinical significance Ion channels : Cystic Fibrosis Transmembrane Receptor (CFTR) as an example Disorders in ion transport can result in severe clinical consequences Cystic Fibrosis is due to defect in the Cl channel CFTR in epithelial - cells Lung congestion and infections 40 2. Function of the plasma membrane Transport Active Transport: Clinical significance Ion channels : CFTR as an example NORMAL (Hydrated mucus) CYSTIC FIBROSIS (Dehydrated mucus leading to chronic lung infections and inflammation, which destroy pulmonary function) 41 Summary Summary: PLASMA MEMBRANE • Lipid bilayer protecting the cell composed of lipids, proteins and carbohydrates • Acts as a semipermeable barrier • Important cell functions take place in the membrane • • • Cell Surface Identity Marker (cell-cell recognition) Cell Surface Receptor (signal transduction) Transport (passive and active transport) Membranes and the proteins associated with them are the target for many drugs 42 Further Reading Biochemistry : Jeremy M. Berg, Lubert Stryer, John Tymoczko, Gregory (8th/9th edition), 2019 Publisher: WH Freeman Molecular Biology of the Cell : Alberts (6th Edition). Zuniga-Hertz JP and Patel HH(2019) The Evolution of Cholesterol-Rich Membrane in Oxygen Adaption: The Respiratory System as a Model. Front. Physiol. 10:1340.doi: 10.3389/fphys.2019.01340. Galea, & Brown 2009 Special relationship between sterols and oxygen: Were sterols an adaptation to aerobic life? Free Radical Biology & Medicine 47 (2009) 880–889 Singer, S. Jonathan, and Garth L. Nicolson. "The fluid mosaic model of the structure of cell membranes." Science 175.4023 (1972): 720-731. Verkman, A. S., et al. "Water transport across mammalian cell membranes." American Journal of Physiology-Cell Physiology270.1 (1996): C12-C30. Heimburg, Thomas. "Physical properties of biological membranes." arXiv preprint arXiv:0902.2454 (2009). https://arxiv.org/abs/0902.2454 Tarbell, John M., and L. M. Cancel. "The glycocalyx and its significance in human medicine." Journal of internal medicine 280.1 (2016): 97-113. 43