Membranes: Structure and Function PDF

Membranes: Their Structure, Function, and Chemistry The Functions of Membranes Models of Membrane Structure: An Experimental Approach  The fluid mosaic model is thought to be descriptive of all biological membranes  The model envisions a membrane as two fluid layers of lipids with proteins w...

Membranes: Their Structure, Function, and Chemistry The Functions of Membranes Models of Membrane Structure: An Experimental Approach  The fluid mosaic model is thought to be descriptive of all biological membranes  The model envisions a membrane as two fluid layers of lipids with proteins within and on the layers  Many important experiments led to understanding of membrane structure and function Overton: Lipids Are Important Components of Membranes  In the 1890s, Charles Overton observed the easy penetration of lipid-soluble substances into cells and concluded that the cell surface had some kind of lipid “coat” on it Langmuir: Phospholipids are amphipathic  Irving Langmuir dissolved phospholipids in benzene and found they formed a single molecule layer on the surface of water Benzene Water You collect 1000 red blood cells with an estimated combined surface area of 8 cm2. You dissolve the plasma membranes of these cells in benzene and layer the phospholipids on the surface of water. What would you predict the surface area of your layered phospholipids to be? A) 8 cm2 B) 4 cm2 C) 80 cm2 D) 16 cm2 E) 64 cm2 Gorter and Grendel: The Basis of Membrane Structure Is a Lipid Bilayer  In 1925, these two physiologists extracted lipids from red blood cells and spread the lipids in a monolayer on a water surface  The film on the water was twice the surface area of the blood cells, suggesting that lipids on the cell surface consisted of two layers  They suggested that the most favorable structure would be a lipid bilayer, with the nonpolar regions of the lipids facing inward Gorter and Grendel: The Basis of Membrane Structure Is a Lipid Bilayer Davson and Danielli: Membranes Also Contain Proteins  Hugh Davson and James Danielli showed that cell membranes had lower surface tension and higher permeability to some polar solutes than a pure lipid film Problems with the Davson-Danielli Model Isolated membrane proteins Globular proteins with sizes and shapes inconsistent with this protein monolayer model Insoluble in water Protein:Lipid ratio varies considerably in membranes from different sources Phospholipases degrade membrane phospholipids rather easily Singer and Nicholson: A Membrane Consists of a Mosaic of Proteins in a Fluid Lipid Bilayer  The fluid mosaic bilayer model accounts for all the inconsistencies with previous models Unwin and Henderson: Most Membrane Proteins Contain Transmembrane Segments  Most integral membrane proteins have one or more hydrophobic segments that span the lipid bilayer Membrane Lipids: The “Fluid” Part of the Model  Membrane lipids are important components of the “fluid” part of the fluid mosaic model  Membranes contain several types of lipids Phospholipids Glycolipids Sterols Phospholipids  Phospholipids are the most abundant lipids in membranes  They include the glycerol-based phosphoglycerides and the sphingosine-based sphingolipids  Phospholipid composition varies in membranes from different sources Glycolipids  Glycolipids are formed by the addition of carbohydrates to lipids  Some are glycerol based (the glycoglycerolipids), and some are sphingosine based (the glycosphingolipids)  The most common glycosphingolipids are cerebrosides and gangliosides Sterols  The membranes of most eukaryotes contain significant amounts of sterols  The main sterol in animal cell membranes is cholesterol, which is needed to stabilize and maintain membranes Membrane Asymmetry: Most Lipids Are Distributed Unequally Between the Two Monolayers  Membrane asymmetry is the difference between the monolayers regarding the kind of lipids present and the degree of saturation of fatty acids in the phospholipids  Most of the glycolipids in the plasma membrane of animal cells are in the outer layer  Membrane asymmetry is established during the synthesis of the membrane Lipids Move Freely Within Their Monolayer Rotation and lateral diffusion are rapid and random Measuring Lipid Mobility with FRAP fluorescence recovery after photobleaching  Investigators label lipid molecules in a membrane with a fluorescent dye  A laser beam is used to bleach the dye in a small area, creating a dark spot on the membrane  The membrane is observed afterward to determine how long it takes for the dark spot to disappear, a measure of how quickly new fluorescent lipids move in Membrane Asymmetry Tends to Be Maintained  transverse diffusion (or “flip-flop”) is relatively rare requires hydrophilic head group to pass through the hydrophobic interior of the membrane Transverse diffusion (flip-flop) is very infrequent in artificial bilayers, yet can be observed more frequently in living biological membranes. What is the explanation for this phenomenon? A) Lipids inhibit the transverse diffusion of nearby lipids. B) Cells probably contain a protein (a flippase) that catalyzes the transverse diffusion of lipids. C) Lipids that are rotating or undergoing lateral diffusion are unable to flip-flop. D) Artificial bilayers have different lipid composition than native biological membranes Membrane Fluidity must be Maintained Factors that regulate membrane fluidity: Temperature fluidity increases as temperature increases Fatty Acid Structure Saturation unsaturated fatty acids increase membrane fluidity Length of hydrocarbon tail fluidity increases when hydrocarbon length decreases Incorporation of Sterols rigidity of sterol structure reduces membrane fluidity at higher temperatures rigidity of sterol structure also prevents phospholipids from packing too close together and reduces the tendency to gel at cooler temperatures  Temperature Fatty Acid Saturation Differential Scanning Calorimetry: monitors uptake of heat to identify transition from gel to liquid Membrane Proteins: The “Mosaic” Part of the Model  The mosaic part of the fluid mosaic model includes lipid rafts and other lipid domains  However, membrane proteins are the main components Classes of Membrane Proteins 1. Integral membrane proteins are embedded in the lipid bilayer because of their hydrophobic regions 2. Peripheral proteins are hydrophilic and located on the surface of the bilayer 3. Lipid-anchored proteins are hydrophilic and attached to the bilayer by covalent attachments to lipid molecules embedded in the bilayer Which of the above integral membrane proteins displays clear quaternary structure? A B C D Classes of Membrane Proteins Membrane-Spanning Structures α-helix β-barrel Membrane Proteins Are Oriented Asymmetrically Across the Lipid Bilayer  Membrane proteins exhibit asymmetric orientation with respect to the lipid bilayer  Once in place, in or on one of the monolayers, proteins cannot move across the membrane from one surface to the other  All the molecules of a particular protein are oriented the same way in the membrane Many Membrane Proteins Are Glycosylated  Glycoproteins are membrane proteins with carbohydrate chains covalently linked to amino acid side chains  The addition of a carbohydrate side chain to a protein is called glycosylation  Glycosylation occurs in the ER and Golgi compartments  Glycosylation involves linkage of the carbohydrate to  The nitrogen atom of an amino group (N-linked glycosylation) of an asparagine residue, or  The oxygen atom of a hydroxl group (O-linked glycosylation) of a serine, threonine, or modified lysine or proline residue  Carbohydrate chains attached to peptides can be either straight or branched and range in length from 2 to about 60 sugar units The most common sugars are galactose, mannose, N- acetylglucosamine, and sialic acid