Membrane Structure Transport - European University Cyprus - PDF

Cellular & Molecular Biology MD105 Dr C. Michaeloudes Cell membrane structure and transport Dr C. Michaeloudes Cellular & Molecular Biology MD105  Lecture Objectives To understand: The basic structure and composition of the cell membrane The...

Cellular & Molecular Biology MD105 Dr C. Michaeloudes Cell membrane structure and transport Dr C. Michaeloudes Cellular & Molecular Biology MD105  Lecture Objectives To understand: The basic structure and composition of the cell membrane The structure of the lipid bilayer and the factors determining its fluidity The different mechanisms by which molecules are transported across the cell membrane Cell membrane structure and composition Cell membrane Protective layer around all cells Made of lipids, proteins and carbohydrates Semi-permeable – some molecules can go through and some not  Cell membrane composition Lipids (40%): Phospholipids and cholesterol arranged in two layers (bilayer) Proteins (50%): embedded in the bilayer performing different functions Carbohydrates (10%): attached to proteins (glycoproteins) and lipids (glycolipids) and extend out of the membrane surface Organelle membranes have lipid bilayer Golgi ER Lysosome Nucleus Mitochondrion Double lipid bilayer Single lipid bilayer Intracellular organelles are also surrounded by membranes with a lipid bilayer structure § Slightly different compositions than cell membrane Nucleus and mitochondria have two lipid bilayers Endoplasmic reticulum, Golgi and lysosomes have one lipid bilayer Lipid bilayer structure Phospholipids and cholesterol Phospholipids Cholesterol Hydrophilic head Hydrophobic tail Main constituents of cell membranes  Cell membrane lipid bilayer Hydrophilic Water head Lipid bilayer Hydrophobic tail Water Membrane lipids are exposed to two opposite forces: § The hydrophilic head is attracted to water § The hydrophobic tails aggregate away from water Formation of bilayer: § Hydrophilic heads face the water on both surfaces of the bilayer § Hydrophobic tails stay within the bilayer interior Image from Essential Cell Biology, 5th Edition  Cell membrane fluidity Membrane lipids and proteins have the ability to move freely inside the membrane This gives the cell membrane a fluid structure Image from Dzikovski, B., Freed, J. (2013). Membrane Fluidity. Doi: 10.1007/978-3-642-16712-6_546  Cell membrane phospholipid movement Lateral diffusion Hydrocarbon tails Movement from monolayer to the other - very rare (flip-flop) Flexion Rotation Phospholipids move and change places with one another within the same monolayer (lateral diffusion) – catalyzed by enzymes § Very rarely they move from one monolayer to the other (flip-flop) Lipid molecules flex their hydrocarbon tails and rotate rapidly around their long axis Fluidity depends on how tightly packed the hydrocarbon tails § Tightly packed tails form hydrophobic interactions between them preventing movement Image from Essential Cell Biology, 5th Edition Cell membrane phospholipid movement Factors determining cell membrane fluidity 1. Temperature 2. Chemical structure of phospholipid tail 3. Cholesterol levels Effect of temperature on cell membrane fluidity High temperature Low temperature At high temperatures At low temperatures phospholipids phospholipids have more have less energy so show less energy to move movement § They move more leading § They are more tightly packed to more spaces between leading to hydrophobic them interactions between them § Increased fluidity § Decreased membrane fluidity Images from www.cytochemistry.net/cell-biology/membrane.htm  REMINDER – Saturated vs unsaturated fatty acids Saturated fatty acid Saturated fatty acids: only single bonds between carbons in the hydrocarbon chain (no double bonds) § “Straight” structure – no “bending” § Fatty acids can pack tightly next to each other forming interactions – usually solid at room temperature https://www.khanacademy.org/science/biology/macromolecules/lipids/a/lipids  REMINDER – Saturated vs unsaturated fatty acids Cis-unsaturated Trans-unsaturated Unsaturated fatty acids: one or more double bonds between carbons in the hydrocarbon chain Cis-unsaturated fatty acids – hydrogen atoms on the same side of the double bond § The chain is bent - creates space between fatty acid chains § Creates space between tails leading to less interactions - liquid at RT Trans-unsaturated fatty acids – hydrogen atoms on different sides of the double bond https://www.khanacademy.org/science § Chain is straight – solid at RT /biology/macromolecules/lipids/a/lipids  Phospholipid tails contain saturated and unsaturated fatty acids Phospholipid tails consist of two fatty acids § They can be saturated or Cis-unsaturated unsaturated Double bonds Saturated Bent structure Cis-unsaturated fatty acids are bent No double so they cannot pack tightly bonds together Straight structure § More space between them § Form less interactions between them § More movement and fluidity Image from Essential Cell Biology, 5th Edition  Effect of phospholipid structure on cell membrane fluidity Fluid Viscous Unsaturated hydrocarbon Saturated hydrocarbon tails with bents tails Length of hydrocarbon chain § Short hydrocarbon tails less interact less with each other increasing fluidity Double bonds in hydrocarbon chain § Hydrocarbon tails with double bonds are bent creating more space - increasing fluidity  Effect of cholesterol on cell membrane fluidity Cholesterol fits in the spaces between phospholipid molecules and regulates membrane fluidity Cholesterol acts as a buffer to prevent extreme changes in cell membrane fluidity at low and high temperatures § At low temperatures it increases fluidity and prevents freezing § At high temperatures it reduces fluidity and prevents melting  Effect of cholesterol on cell membrane fluidity Low temperature High temperature Phospholipids are tightly Phospholipids are loosely packed packed Cholesterol prevents Cholesterol reduces the spaces phospholipids from packing between phospholipids tightly preventing their movement Increased fluidity Reduced fluidity  Importance of cell membrane fluidity Membrane proteins Cell division Vesicle-lysosome fusion Cell membrane fluidity allows the cell to adapt its shape and movement to different conditions: § Enables membrane proteins to diffuse in the lipid bilayer and interact with each other - important for cell signalling Ensures membrane molecules are distributed evenly between daughter cells when the cell divides Allows membranes to fuse with each other and mix their molecules Ø E.g fusion of vesicles Membrane proteins and carbohydrates  Membrane proteins Peripheral protein Integral proteins Proteins are ”stuck” inside the (transmembrane) membrane § Fluid structure with proteins embedded in it - “fluid mosaic model” Membrane proteins are either: § Integral proteins: Embedded inside Integral the hydrophobic core of the lipid Peripheral proteins proteins bilayer or span the membrane (transmembrane) § Peripheral proteins: Attached to the surface of the membrane  Membrane protein functions Glycoprotein: protein with Glycolipid: lipid with carbohydrate attached carbohydrate attached Receptor protein Enzyme Phospholipid Anchor Cholesterol Transporter bilayer protein Cytoskeleton protein Proteins perform the main functions of the membrane § Transporters – movement of ions and macromolecules in/out of the cells § Receptors – detecting chemical signals from the environment § Enzymes – chemical reaction catalysts § Anchors – connect the cell membrane to the cytoskeleton (structural support)  Membrane carbohydrates Glycoprotein: protein with carbohydrate Glycolipid: lipid with attached carbohydrate attached Receptor protein Enzyme Phospholipid Anchor Cholestero Transporte bilayer protein Cytoskeleton l r protein Some lipids on the outer surface of the membrane have sugars attached to them by covalent bonding - glycolipids Most cell membrane proteins have sugars attached to them § Short chains of sugars (oligosaccharides) – glycoproteins § Long polysaccharides - proteoglycans § Important for damage protection, lubrication and cell-cell recognition Membrane transport proteins The cell membrane is semi-permeable The hydrophobic interior of the lipid bilayer prevents the passage of most hydrophilic molecules Lipid bilayer is selective: § Small non-polar (hydrophobic) molecules (O2, CO2, N2, steroid hormones) cross the membrane rapidly § Small polar (hydrophilic) molecules (H2O, ethanol) cross very slowly § Large polar (hydrophilic) molecules (glucose, amino acids) cross extremely slowly if at all – require transporter proteins § Ions cannot cross at all - require transporter proteins  Transport proteins Cells and organelles must allow the passage of many hydrophilic molecules such as inorganic ions, sugars, amino acids, nucleotides § Important for metabolism and function Cell use transport proteins to move these molecules across the membrane Types of transport proteins: 1. Channels: allow ions of a particular size and charge to pass 2. Transporters: transport molecules that fit to specific binding sites on the protein (i.e similar to enzyme-substrate binding)  Transport proteins Channels Allow ions of a particular size and charge to pass § e.g Na+ but not K+ Open or closed conformation § Need to be open to allow passage § Controlled by signalling cascades Transporters Allows movement of molecules that fit in binding site (solutes) Very specific for the solute § Like enzyme-substrate  Types of ion channels Voltage-gated channels contain voltage sensor domains that allow them to open in response to changes in membrane potential Ligand-gated channels are controlled by the binding of a molecule (ligand) to the channel § E.g activated by neurotransmitters like acetylcholine at neuronal synapses Mechanically-gated channels are controlled by a mechanical force acting on the channel § E.g auditory hair cells in the ear that sense vibrations  Types of ion channels Voltage- Ligand-gated Ligand-gated Mechanically- gated (extracellular (intracellular gated ligand) ligand)  Resting membrane potential Lipid bilayer is not permeable to ions § Differences in the concentrations of ions between inside and outside the cell § High concentrations of Na+, Ca2+ and Cl- outside the cells § High concentrations of K+ and organic anions (amino acids/proteins) inside the cells Small differences in the concentrations of negatively and positively- charged ions § Slightly more negative inside the cell This creates a voltage difference across the membrane called resting membrane potential (-20 to -200mV) Stored energy that can be used for cell functions  Resting membrane potential + + + + +++++ + ++ + + + + + + + + - - --- - - - - - - - - - - - - - - - - Resting membrane potential = -20 to 200mV Image adapted from https://openbooks.lib.msu.edu/neuroscience/chapter/the-membrane-at-rest/ Mechanisms of membrane transport  Concentration gradient Concentration gradient = difference in the concentration of a substance across a membrane Concentration gradient contains stored energy that drives the movement of molecules across the membrane – diffusion Diffusion stops when concentration on both sides of the membrane is the same Image from https://study.com/learn/lesson/concentration-gradient-examples.html  Passive transport Molecule Channel Transporter Cell membrane Concentration gradient Simple diffusion Facilitated diffusion Molecules move from regions of high concentration to regions of low concentration without needing energy - along a concentration-gradient Two types of passive transport: 1. Simple diffusion: Molecules directly cross the lipid bilayer Ø Small non-polar molecules like gases (e.g O2, CO2) 2. Facilitated diffusion: Molecules cross the lipid bilayer with the help of membrane transport proteins Ø Large polar molecules (e.g glucose, amino acids, nucleotides) and ions  Passive transport of charged molecules For uncharged or polar molecules only concentration gradients determine the direction of passive transport For charged molecules like inorganic ions and small organic ions there are 2 forces that determine the direction of passive transport : 1. Resting membrane potential: inside the cell membrane is more negatively charged so it attracts positively-charged molecules from outside to the inside of the cell 2. Concentration gradient: charged molecules move from areas of high concentration to areas of low concentration The net force driving the direction is a combination of the two forces and is called electrochemical gradient  Passive transport of charged molecules Na+ Na+ K+ Na+ Na+ Outside Outside + ++ + +++ ++ + +++ + ++ + +++ ++ + +++ -- ------------- -- ------------- Inside Inside K+ K+ K+ Na+ K+ Concentration gradient and Concentration gradient and membrane potential work in membrane potential work in the same direction opposite directions Na+ flow inside the cell at a K+ flow outside the cell in a slow fast rate rate  Active transport Molecule / Pump Cell Concentration gradient membrane ENERGY ENERGY Molecules move from regions of low concentration to regions of high concentration - against a concentration-gradient Drive movement of molecules ”uphill” – requires energy Facilitated by special transporter proteins called pumps Obtain energy from ATP hydrolysis or energy released from electrochemical gradients Summary of membrane transport  Osmosis Movement of water inside the cell is crucial Direct movement of water across the lipid bilayer is slow § Water is a small polar molecule Some cells contain specialized transport proteins called aquaporins that facilitate the movement of water across the membrane The concentration of solutes (osmolarity) inside cells is greater than outside – concentration gradient Water moves from the area of low solute concentration (outside the cells) to the area of high solute concentration (inside the cell) § This process is called osmosis Osmosis Low solute concentration Osmosis High solute concentration