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Cells and Their Housekeeping Functions – Cell Membrane & Membrane Potential Shu-Ping Lin, Ph.D. Institute of Biomedical Engineering E-mail: [email protected] Website: http://web.nchu.edu.tw/pweb/users/splin/ http://en.wikipedia.org/wiki/Cell_membrane#Lipid_bilayer * Cell membrane, also called plasma membrane, separates cell interior from surroundings Thin barrier = 7~10 nm thick Controls traffic in & out of the cell Selectively permeable * Made of phospholipids, proteins, carbohydrates & other macromolecules *Phospholipids arrange as a bilayer: Hydrophobic fatty acid tails Hydrophilic phosphate group head Phospholipid Bilayer Several important functions: *A. Allow nutrients to enter cell, *B. Keep out unwanted molecules and particles, *C. Transport waste out into extracellular fluid, *D. Prevent needed metabolites and ions from leaving cell Inherently amphipathic nature: possess both hydrophilic & hydrophobic structures polar hydrophilic heads nonpolar hydrophobic tails polar hydrophilic heads http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg More Than Lipids… In 1972, S.J. Singer & G. Nicolson proposed that membrane proteins are inserted into the phospholipid bilayer It’s like a fluid… It’s like a mosaic… It’s the Fluid Mosaic Model! http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion .ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9TuKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Cell membrane is composed of a double layer of phospholipid molecules (called phospholipid or lipid bilayer), protein molecules associated with lipid bilayer, and carbohydratecontaining cell coat called glycocalyx. Glycoprotein Extracellular fluid Glycolipid Phospholipids Cholesterol Peripheral protein Cytoplasm Transmembrane proteins Filaments of cytoskeleton http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Membrane Fat Composition Varies Fat composition affects flexibility membrane must be fluid & flexible about as fluid as thick salad oil % unsaturated fatty acids in phospholipids keep membrane less viscous cold-adapted organisms, like winter wheat increase % in autumn cholesterol in membrane http://www.ocvts.org/instructors/htm/asprague/Biot ech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3sr9wakHHx6SCbBg9TuKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFaf YX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp -LymP07E_VLiGzjkC-wqjHTg Membrane Proteins Proteins determine membrane’s specific functions Cell membrane & organelle membranes each have unique collections of proteins Membrane proteins: Peripheral proteins Loosely bound to surface of membrane Cell surface identity marker (antigens) Integral proteins Penetrate lipid bilayer, usually across whole membrane Transmembrane protein Transport proteins channels, pumps http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Why are proteins the perfect molecule to build structures in the cell membrane? http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Classes of Amino Acids What do these amino acids have in common? nonpolar & hydrophobic http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Classes of Amino Acids What do these amino acids have in common? I like the polar ones the best! polar & hydrophilic http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9TuKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Proteins Domains Anchor Molecule Within membrane Nonpolar amino acids Polar areas of protein Hydrophobic Anchors protein into membrane On outer surfaces of membrane Polar amino acids Hydrophilic Extend into extracellular fluid & into cytosol Nonpolar areas of protein http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Many Functions of Membrane Proteins Outside Plasma membrane Inside Transporter Enzyme activity Cell surface identity marker Cell adhesion Cell surface receptor Attachment to the cytoskeleton http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Membrane Carbohydrates The carbohydrates are not inserted into the membrane -- they are too hydrophilic for that. They are attached to embedded proteins -- glycoproteins. Play a key role in cell-cell recognition Ability of a cell to distinguish one cell from another Antigens Important in organ & tissue development Basis for rejection of foreign cells by immune system http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+p pt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQ-GCRtlnAD5GIlGBWSBEKRBkJwIU3sr9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Movement Across the Cell Membrane http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Selectively Permeable What molecules can get through directly? Small nonpolar molecules such as carbon dioxide, nitrogen, and oxygen diffuse freely across the bilayer. Lipid bilayer is also permeable to small and uncharged polar molecules such as urea and ethanol. Other small hydrophobic molecules: fats and other lipids NOT get through directly? Ions: salts, ammonia (NH3) Large uncharged or charged polar molecules: starches, proteins H2O molecule has 2 pathways: Lipid pathway Water channel-protein pathway (polar molecules) Diffusion Across Cell Membrane Cell membrane is the boundary between inside & outside… Separates cell from its environment Can it be an impenetrable boundary? NO! OUT IN food carbohydrates sugars, proteins amino acids lipids salts, O2, H2O OUT IN waste ammonia salts CO2 H2 O products cell needs materials in & products or waste out http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Diffusion 2nd Law of Thermodynamics governs biological systems universe tends towards disorder (entropy) Diffusion movement from high low concentration http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Diffusion Move from HIGH to LOW concentration “passive transport” no energy needed Osmotic pressure: the pressure is required to stop the net flow of water across a membrane separating solutions of different particulate concentration diffusion movement of water osmosis http://www.ocvts.org/instructors /htm/asprague/Biotech/Ch06Cell MembraneDiffusion.ppt+cell+mem brane+ppt&hl=zhTW&gl=tw&pid=bl&srcid=ADGEES hywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3 s-r9wakHHx6SCbBg9TuKL7xUvpYTtYHO3iB1SQtH0eo8bD 2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFR csI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Zero flux The Special Case of Water: Movement of water across the cell membrane 2007-2008 http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Osmosis Osmosis is diffusion of water Diffusion of water from high concentration of water to low concentration of water across a semi-permeable membrane http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt +cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9TuKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafYX0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRp-LymP07E_VLiGzjkC-wqjHTg Concentration of Water Direction of osmosis is determined by comparing total solute concentrations Hypertonic - more solute, less water Hypotonic - less solute, more water Isotonic - equal solute, equal water water hypotonic hypertonic net movement of water http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Effect of Osmotic Pressure Suppose an animal or a plant cell is placed in a solution of sugar or salt in water. If the medium is hypotonic — a dilute solution, with a higher water concentration than the cell The cell will gain water and wilt through osmosis. If the medium is isotonic — a solution with exactly the same water concentration as the cell There will be no net movement of water across the cell membrane. If the medium is hypertonic — a concentrated solution, with a lower water concentration than the cell The cell will lose water and shrink by osmosis. http://en.wikipedia.org/wiki/Osmosis Managing Water Balance Cell survival depends on balancing water uptake & loss freshwater balanced saltwater Animal cells culture: must maintain in isotonic cell culture medium (concentration of solutes is close to cell cytoplasm) http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Aquaporins 1991 | 2003 Cores of these channel proteins are hydrophilic Water moves rapidly into & out of cells Multiple water molecules pass through membrane at a rate of 108 molecules/sec Evidence that there were water channels Peter Agre John Hopkins Roderick MacKinnon Rockefeller http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Channels Through Cell Membrane Membrane becomes semi-permeable with protein channels specific channels allow specific material across cell membrane inside cell NH3 H 2O salt aa sugar outside cell http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Facilitated Diffusion Diffusion through protein channels Channels move specific molecules across cell membrane facilitated = with help No energy needed open channel = fast transport high low “The Bouncer” http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Active Transport Cells may need to move molecules against concentration gradient Shape change transports solute from one side of membrane to other Protein “pump” “Costs” energy = ATP conformational change high ATP low “The Doorman” http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Many Models & Mechanisms of Active Transport Ions and polar molecules across cell membranes include: ATP-powered pumps Transporter proteins Ion channels The arrows indicate the direction from high to low concentration of the ion or polar molecule across membrane high low high low low high Getting through cell membrane Passive Transport Simple diffusion diffusion of nonpolar, hydrophobic molecules Facilitated transport diffusion of polar, hydrophilic molecules through a protein channel lipids high low concentration gradient high low concentration gradient Active transport diffusion against concentration gradient low high uses a protein pump requires ATP ATP Transport Summary simple diffusion facilitated diffusion active transport ATP http://www.ocvts.org/instructors/htm/asprague/Biotech/Ch06CellMembraneDiffusion.ppt+cell+membrane+ppt&hl=zh-TW&gl=tw&pid=bl&srcid=ADGEEShywZ9NflQGCRtlnAD5GIlGBWSBEKRBkJwIU3s-r9wakHHx6SCbBg9T-uKL7xUvpYTtYHO3iB1SQtH0eo8bD2ZhKGcUlBOZBeeFafY-X0MbAXuEr5KIF3tINko9uVQlhxFRcsI&sig=AHIEtbTYRpLymP07E_VLiGzjkC-wqjHTg Active Transport- Na+-K+ Pump Sodium ion binds to transport protein in configuration 1 ATP molecule associates with transport protein After ATP hydrolysis, phosphate group is transferred to transport protein Causing to switch of configuration 2 Sodium ion is released to the outside of cell Potassium ion is bound to attachment site of transport protein Binding of potassium ion Result in the release of phosphate group Protein goes back to configuration 1 Potassium ion is released into cell Cycle is completed with the attachment of sodium ion into cavity of transport protein Active Transport- Proton Pump Proton pumps, in a lysosomal membrane, are used by plants, bacteria, and fungi to create electrochemical gradients (sodium-potassium pumps are employed by animals for the same purpose) www.mansfield.ohio-state.edu/~sabedon/lectures/.../campbl08.ppt Examples Retinal chromophore H+ NH2 Water channel in bacteria Porin monomer b-pleated sheets Bacterial outer membrane Nonpolar (hydrophobic) a-helices in the cell membrane COOH H+ Cytoplasm proton pump channel in photosynthetic bacteria function through conformational change = shape change Membrane Electrical Potential Membrane potential: The electrical charge across a cell membrane; the difference in electrical potential inside and outside the cell. Axons have two basic electrical potentials: 1. Resting membrane potential: The membrane potential of a neuron when it is not being altered by excitatory or inhibitory postsynaptic potentials. 2. Action potential: The brief electrical impulse that provides the basis for conduction of information along an axon. www.psych.yorku.ca/desouza/PSYC3250/M/class2/Lecture2.../Lecture2.ppt Electrochemical Gradient • An Electrochemical Gradient is a Concentration Gradient with Ions: - These ions want to move down their concentration gradient - These ions (particularly) also want to move towards the opposite charge found on the other side of the membrane - This attraction for the other side of membranes (membrane potential) can be harnessed to do work - Electrochemical gradients essentially are batteries, i.e., means of physically storing electrical energy www.mansfield.ohio-state.edu/~sabedon/lectures/.../campbl08.ppt