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Biological Membranes Basic framework of the membrane is the phospholipid bilayer Phospholipids are amphipathic molecules Hydrophobic (water-fearing) region faces in Hydrophilic (water-loving) region faces out Membranes also contain proteins and carbohydrates Relative amount of each vary 1 Fluid-mosaic model Membrane is considered a mosaic of lipid, protein, and carbohydrate molecules Membrane exhibits properties that resemble a fluid because lipids and proteins can move relative to each other within the membrane 2 3 Proteins bound to membranes Integral membrane proteins Transmembrane One or more regions that are physically embedded in the hydrophobic region of the phospholipid bilayer Lipid proteins anchors Covalent attachment of a lipid to an amino acid side chain within a protein Peripheral membrane proteins Noncovalently bound to regions of integral membrane proteins that project out from the membrane, or they are bound to the polar head groups of phospholipids 4 5 Approximately 25% of All Genes Encode Membrane Proteins Membranes are important biologically and medically Computer programs can be used to predict the number of membrane proteins Estimated percentage of membrane proteins is substantial: 20–30% of all genes may encode membrane proteins This trend is found throughout all domains of life including archaea, bacteria, and eukaryotes Function of many genes unknown- study may provide better understanding and better treatments Membranes are semifluid Fluidity- individual molecules remain in close association yet have the ability to readily move within the membrane Semifluid- most lipids can rotate freely around their long axes and move laterally within the membrane leaflet “Flipflop” of lipids from one leaflet to the opposite leaflet does not occur spontaneously Flippase requires ATP to transport lipids from one leaflet to another 8 9 Factors affecting fluidity Length of fatty acyl tails Shorter acyl tails are less likely to interact, which makes the membrane more fluid Presence of double bonds in the acyl tails Double bond creates a kink in the fatty acyl tail, making it more difficult for neighboring tails to interact and making the bilayer more fluid Presence of cholesterol Cholesterol tends to stabilize membranes Effects depend on temperature 10 Experiments on lateral transport Larry Frye and Michael Edidin conducted an experiment that verified the lateral movement of membrane proteins Mouse and human cells were fused Temperature treatment- 0°C or 37°C Mouse membrane protein H-2 fluorescently labeled 0°C cells- label stays on mouse side 37°C cells- label moves over entire cell 11 12 Not all integral membrane proteins can move Depending on the cell type, 10–70% of membrane proteins may be restricted in their movement Integral membrane proteins may be bound to components of the cytoskeleton, which restricts the proteins from moving laterally Also, membrane proteins may be attached to molecules that are outside the cell, such as the interconnected network of proteins that forms the extracellular matrix 13 14 Glycosylation Process of covalently attaching a carbohydrate to a protein or lipid Glycolipid – carbohydrate to lipid Glycoprotein – carbohydrate to protein Can serve as recognition signals for other cellular proteins Often play a role in cell surface recognition Protective effects Cell coat or glycocalyx - carbohydrate-rich zone on the cell surface shielding cell 15 16 Phospholipid bilayer is a barrier Hydrophobic interior makes formidable barrier Diffusion Movement of solute from an area of higher concentration to an area of lower concentration Passive diffusion- without transport protein Solutes vary in their rates of penetration 17 18 Selectively permeable Structure ensures … Essential molecules enter Metabolic intermediates remain Waste products exit 19 Cells maintain gradients Transmembrane gradient Concentration of a solute is higher on one side of a membrane than the other Ion electrochemical gradient Both an electrical gradient and chemical gradient 20 Passive transport Passive transport does not require an input of energy 2 types Passive diffusion Diffusion of a solute through a membrane without transport protein Facilitated diffusion Diffusion of a solute through a membrane with the aid of a transport protein 21 22 Tonicity Isotonic Equal water and solute concentrations on either side of the membrane Hypertonic Solute concentration is higher (and water concentration lower) on one side of the membrane Hypotonic Solute concentration is lower (and water concentration higher) on one side of the membrane 23 Outside the cell Inside the cell Isotonic The solution and cell are isotonic Hypertonic The solution is hypertonic to the cell Hypotonic The solution is hypotonic to the cell 24 Osmosis Water diffuses through a membrane from an area with more water to an area with less water If the solutes cannot move, water movement can make the cell shrink or swell as water leaves or enters the cell Osmotic pressure- the tendency for water to move into any cell 25 Animal cells must maintain a balance between extracellular and intracellular solute concentrations to maintain their size and shape Crenation- shrinking in a hypertonic solution 26 A cell wall prevents major changes in cell size Turgor pressurepushes plasma membrane against cell wall Maintains shape and size Plasmolysis- plants wilt because water leaves plant cells 27 28 Aquaporins Peter Agre and his colleagues first identified, accidentally, a protein that was abundant in red blood cells and kidney cells, but not found in many other cell types CHIP28 Striking difference was observed between frog oocytes that expressed CHIP28 versus the control Aquaporins 29 Aquaporin Discovered accidently in 1992 by Dr. Peter Agre at Johns Hopkins University while looking for Rh factors on RBC Dr. Agre won the Nobel Prize in 2003 …and we met him in 2009! Left to right: Wei Dong, Robin Bagley, Nobel Laureate Dr. Peter Agre, Samantha Mahmoud and Joanna John 30 Transport proteins Transport proteins enable biological membranes to be selectively permeable 2 classes Channels Transporters 32 Channels Form an open passageway for the direct diffusion of ions or molecules across the membrane Aquaporins 33 Most are gatedopen or close Ligand-gated Intracellular regulatory proteins Phosphorylation Voltage-gated Mechanosensitive channels 34 Transporters Also known as carriers Conformational change transports solute Principal pathway for the uptake of organic molecules, such as sugars, amino acids, and nucleotides Key role in export 35 Transporter types Uniporter single molecule or ion Symporter/ cotransporter 2 or more ions or molecules transported in same direction Antiporter 2 or more ions or molecules transported in opposite directions 36 Pump Couples conformational changes to an energy source ATP-driven pumps ATP hydrolysis can be uniporters, symporters, or antiporters Active transport 37 Active transport Movement of a solute across a membrane against its gradient from a region of low concentration to higher concentration Energetically unfavorable and requires the input of energy Primary active transport Directly use energy to transport solute Secondary active transport Use pre-existing gradient to drive transport of solute 38 39 ATP-Driven Ion Pumps Generate Ion Electrochemical Gradients Na+/K+-ATPase transport Na+ and K+ against their gradients by using the energy from ATP hydrolysis 3 Na+ exported for 2 K+ imported into cell Actively Antiporter Electrogenic pump- export 1 net positive charge 40 41 Exocytosis/ Endocytosis Transport larger molecules such as proteins and polysaccharides, and even very large particles Exocytosis Material inside the cell, which is packaged into vesicles, is excreted into the extracellular medium Endocytosis Plasma membrane invaginates, or folds inward, to form a vesicle that brings substances into the cell Receptor-mediated endocytosis Pinocytosis Phagocytosis 42 43 44 KU Game Day!! 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