Biological Membrane PDF

Biological Membrane Cell structure (Eukaryotic) - Cell membrane - Nucleus - Organelles - Cytoplasm - Mitochondria - Cytoskeleton Cell membrane functions 1. Separate inside from outside 2. Maintain concentration gradients 3. Maintain membrane pot...

Biological Membrane Cell structure (Eukaryotic) - Cell membrane - Nucleus - Organelles - Cytoplasm - Mitochondria - Cytoskeleton Cell membrane functions 1. Separate inside from outside 2. Maintain concentration gradients 3. Maintain membrane potential 4. Bind cells together 5. Mediate and regulate cell transport 6. Detect and transmit electrical and chemical signals Cell membrane theory evolution - Overton (1890s): lipid nature of biological membrane - Langmuir (1917): lipid monolayer (hydrophilic/hydrophobic surfaces) - Gorter and Grendel (1925): lipid bilayer - Danielli and Davson (1935): lipid bilayer + protein sheets (“sandwich” model) - Singer and Nicolson (1972): fluid-mosaic theory - Unwin and Henderson (1975): Membrane proteins contain transmembrane segments - Recent Findings (2000): Lipid rafts Cell Membrane (7-10nm) - “Fluid Mosaic Theory” - Singer and Nicolson, 1972 1. Membrane Lipids (40%) a. Bilayer b. Phospholipids – dominate the structure c. Cholesterol – provides stability of the structure 2. Membrane Proteins (52%) a. Peripheral proteins (confined to the surface)  b. Integral proteins (span the membrane) 3. Membrane carbohydrates (8%) a. Glycoproteins b. Glycolipids – provide interaction with other cells Membrane Lipids (40%) - Structure of the membrane - Barrier - Provide fluidity of the membrane - Cholesterol stabilizes the membrane and changes fluidity - Aggregates of lipids + cholesterol forms “lipid rafts” - Phospholipids are the basic components of all biological membranes both prokaryotes and eukaryotes - Phospholipids are amphipathic molecules - One portion of the molecule is water-soluble, and another is lipid soluble - Phospholipids have hydrophilic head groups and long hydrophobic hydrocarbon tail - Hydrophilic head groups contain phosphate (phosphate ion which is different from the element) - In water, phospholipids spontaneously aggregate into a bilayer with the phosphate head groups on the outside - Phosphate groups are in contact with water and hydrocarbon tails contact each other - Phospholipid bilayer forms a stable barrier between two aqueous environments Decrease C, Decrease S, Increase T ---> Increase Soluble ---> Increase Fluid Increase C, Increase S, Decrease T ---> Increase Gel ---> Decrease Fluid Physical Characteristics of Lipid Bilayer - Limited permeability to ions - High electrical resistance - Ability for self-healing - Small force easily transforms bilayers into different shapes - Membrane area is constant, and membrane folds can be formed - Cell swelling forms a sphere that may burst - Cytoplasmic lipid-binding proteins can uptake a lipid from a membrane - Proteins can transfer the lipid  - Lipids can be transferred to another membrane or between the organelles Nanoworld and Biological Membrane Brief review - Lipids spontaneously in microseconds self-assemble into ordered bilayer structures - Bilayer formation is favored (energetically (----> min S) - Strong hydrophobic chains interact and exclude water from the core of the bilayer Membrane lipid composition of a cell (eukaryotic cell) - very complex - Membranes are composed of 500-1000 different lipid species - Hundreds of minor classes - Variations in head group, chain length, and saturation/desaturation Membrane Lipids (40%) sol) o Long-chain FA (> C atoms) decrease membrane fluidity (>gel) - Degree of saturation affects fluidity o Unsaturated FA increase membrane fluidity (>sol) o Saturated FA decrease membrane fluidity (>gel) Temperature Effect (SAME AS ABOVE JUST WORDED DIFFERENT) - Temperature change affects fluidity - Transition temperature Tm - Temperature increase ---> increases membrane fluidity (>sol) - Temperature decrease ---> decrease membrane fluidity (>gel) Cholesterol - Polar head group - Rigid steroid ring (4 rings) - Cholesterol polar head attached to polar head of a FA - Cholesterol nonpolar hydrocarbon tail attached to cis-double bond hydrocarbon tail - Cholesterol stiffens a region on a FA/stabilizes the membrane/changes fluidity  - The main sterol in animal cells - Not found in bacteria - Not found in the inner membrane of mitochondria - Head groups provide distinct properties to different phosphoglycerates - Head groups have a negative charge on the phosphate Cholesterol operates as a fluidity buffer CONFUSED!! - Decreases membrane fluidity at temperatures above Tm - Increases membrane fluidity at temperatures below Tm - Sterols also decrease the membrane permeability to ions and small molecules - Tm = temperature of modification/transition temperature Lipid rafts - Membrane lipids are not uniformly fluid - Lipid rafts are found in outer and inner membranes - Thicker (1-2nm) and less fluid than the surrounding membrane - Characterized by highly saturated phospholipids - Characterized by tightly packed with cholesterol - Dynamic structures that change their composition - Lipid rafts of outer membrane/inner membranes interact - Three types of lipid rafts were described Lipid rafts functions - Cholesterol transport - Endocytosis - Signal transduction - Contain kinases generating second messengers - Sequester signal proteins Membrane proteins (52%) - Integral proteins covalently attached to lipids by hydrophobic transmembrane segments - Peripheral proteins attached to the polar heads by electrostatic forces and hydrogen bonds 1. Ion channels 2. Carrier proteins 3. Receptor sites 4. Electron carriers  5. Membrane bound enzymes 6. Cell adhesion molecules (cams) 7. Stabilize the membrane 8. Detect external signals 9. Transduce external signals - Need to apply 70-150 kcal to disrupt covalent bonds, 3kcal to disrupt electrostatic forces, and 1-4 kcal to disrupt hydrogen bonds Integral proteins - Covalently attached to a fatty acid chain in the hydrophobic interior - Hydrophobic amino acids (20-30) anchor proteins to the membrane - Hydrophilic segments protrude from both sides of the bilayer - Transmembrane segments are typically a-helical sequences of amino acids - Hydrophilic extracellular amino (NH3+) terminus - Hydrophilic cytosolic carboxyl (COO-) terminus - Single pass proteins - Multi pass proteins - Multi subunit proteins Peripheral proteins - Attached to the polar heads by weak electrostatic forces and hydrogen bonds - Attached to hydrophilic portion of proteins or polar heads of membrane lipids - Lack hydrophobic sequences - Many peripheral proteins bind (associate) with integral membrane proteins - Peripheral proteins may attach to the inner surface - form a skeletal meshwork *Note that covalent is the strongest, and hydrogen is the weakest Lipid-anchored membrane proteins - Peripheral proteins o No transmembrane regions o Located on one of the bilayer surfaces o Covalently bound with lipid molecules ▪ Fatty acid-anchored membrane proteins A protein is synthesized int eh cytosol Covalently attached to saturated fatty acids or isoprenyl group on the inner layer  ▪ GPI-anchored membrane proteins Covalently attached to glycosylphosphophatidylinositol (GPI) GPI is a glycolipid found in the outer layer of the plasma membrane GPI proteins are produced in the ER as a singlepass transmembrane protein Protein movements (diffusion) in the membrane - Protein movement (diffusion) may be lateral and rotational (more restricted in movement than phospholipids – can’t do flexion or flip flop) - Lateral movement is temperature dependent – decreases with temperature drop - Some proteins, especially integral proteins, are constrained in their movement - Membrane proteins often function as large complexes - Large complexes may include 19 protein subunits and over 60 transmembrane a- helices Protein complexes - Membrane proteins often function as large complexes - Large complexes participate in proton pumping and electron transport - Large complexes participate in energy transformation - Large complexes participate in extra/intracellular signal transduction Membrane carbohydrates - Glycoproteins - Glycolipids 1. Form glycoproteins and glycolipids 2. Orientate membrane proteins 3. Provide cell-cell interaction 4. Act as receptors 5. Involve in immune reactions 6. Important in cell recognition 7. Abundant in the plasma membrane of eukaryotes 8. Practically absent from most intracellular membranes Glycoproteins - Carbohydrate side chain is added to the protein (glycosylation) - Carbohydrate to nitrogen (amino group) - (n-linked glycosylation) - asparagine  - Carbohydrate to oxygen (hydroxyl group) - (o-linked glycosylation) - serine or threonine - Carbohydrate chain either straight or branched - Length from 2 to 60 sugar units - Common sugars – galactose, mannose, N-acetylglucosamine Glycolipids - Found in lower concentrations - Carbohydrate side chain is orientated outside the cell - Blood groups antigens - Receptors for some toxins (tetanus and cholera) Cell membrane cell to cell adhesion 1. Extracellular matrix (ECM) - Protein fibers secreted by fibroblasts: o Collagen o Elastin o Fibronectin 2. Specialized cell junctions - Tight junctions - Desmosomes (plaques held together by linker proteins – 20nm space) - Gap junctions (connecting tunnels – connexons diameter: 1.5 nm)