National University of Science and Technology Faculty of Medicine Division of Biomedical Sciences MBM 1001 Biochemistry: M EMBRANE STRUCTURE AND FUNCTION Lecturer: Ms. P. Tizora
This lecture Biological membranes: Summary of functions and major components – lipids, proteins and carbohydrates; the fluid mosaic model, macromolecular motion, asymmetry of membrane.
Biological membranes Biological membranes have structure comprised of lipids, proteins and carbohydrates These molecules are responsible for the structure – the way the membrane is organised and ultimately its function What is the function of the cell membrane?
Cell membrane function Protect the cell from its environment Each cell must maintain its integrity in various environments Selective permeability is important The plasma membrane surrounds each cell and separates it from other cells as a distinct entity Organelles within a cell are also membrane bound separating vital incompatible chemical reactions from each other
Summary 3 primary functions Acts as a protective barrier, keep toxins out of the cell and keeps the cell constituents in the cell Acts as a gate permitting specific molecules, such as ions, nutrients into the cell and wastes, and metabolic products out of the cell Separate vital but incompatible metabolic processes conducted within organelles
Lipids in the membrane are generally phospholipids and sterols (cholesterol) These lipids have dual characteristics, being readily soluble in organic solvents. But additionally possessing a region that is attracted to and soluble in water They are amphiphilic This property is the basis of the structure of cell membranes lipids, proteins and carbohydrates
Lipids Phospholipid is made of a hydrophilic head- usually glycerol with a phosphoryl group attached and two fatty acid tails In water form liposomes
sterols have a complex hydrocarbon ring structure as the lipid-soluble region and a hydroxyl grouping as the water-soluble region . structure of cholesterol is such that it does not form aggregates in water , found in between phospholipids in membrane, with its OH group located at the water-membrane interface. The stiff fused ring structure of cholesterol adds rigidity to liquid-crystalline phospholipid bilayers and strengthens them against mechanical rupture Lipids
Fatty Acids Saturated - no double bonds Unsaturated - at least one double bond Cis double bond
Sphingomyelin Non-polar Tails Polar End
Lipids Liposomes
Lipids Glycolipids Glycolipids probably occur in all animal cell plasma membranes, where they generally constitute about 5% of the lipid molecules in the outer monolayer . Immunological properties.
S phingomyelin sphingomyelin, a molecule with a phosphorylcholine group (the same polar head group as in phosphatidylcholine) instead of the sugar moiety, making it an analog of phosphatidylcholine. All sphingolipids have, in addition to the sugar, a fatty acid attached to the amino group of sphingosine.
Lipid Movement Across Lipid Bilayer Lateral (within one bilayer) Transverse (from one side to the other)
Lateral Movements Lateral Movements
Transverse Movements Transverse Movements
Cholesterol in the Lipid Bilayer
Membrane Proteins Integral membrane proteins are embedded in the membrane and project through both sides of the lipid bilayer. Peripheral membrane proteins are embedded in or tightly associated with part of the bilayer, but do not project completely through both sides . Associated membrane proteins are found near membranes , but may not be embedded in them . Their association may arise as a result of interaction with other proteins or molecules in the lipid bilayer. Anchored membrane proteins are not themselves embedded in the lipid bilayer, but instead are attached to a molecule (typically a fatty acid) that is embedded in the membrane The amphiphilic nature of the bilayer dictates the amino acid side chains of the proteins that associate with the bilayer
For most membrane proteins, the polar amino acids are found where the protein projects through the bilayer ( interacting with aqueous/polar substances) and the non-polar amino acids are embedded within the non-polar portion of the bilayer containing the fatty acid tails. Glycolipids and glycoproteins play important roles in cellular identification . Blood types, for example, differ from each other in the structure of the carbohydrate chains projecting out from the surface of the glycoprotein in their membranes. Cells have hundreds of membrane proteins and the protein composition of a membrane varies with its function and location. Mitochondrial membranes are among the most densely packed with proteins. The plasma membrane has a large number of integral proteins involved in communicating information across the membrane ( signalling ) or in transporting materials into the cell
Structure of integral membrane proteins : Integral membrane proteins may have one or more alpha-helices that span the membrane (examples 1 and 2), or they may have beta-sheets that span the membrane (example 3).
Carbohydrates Carbohydrates are the third major component of plasma membranes. found on the exterior surface of cells and are bound either to proteins (forming glycoproteins) or to lipids (forming glycolipids). These carbohydrate chains may consist of 2–60 monosaccharide units and can be either straight or branched. Along with peripheral proteins, carbohydrates form specialized sites on the cell surface that allow cells to recognize each other. This recognition function is very important to cells, as it allows the immune system to differentiate between body cells (called “self”) and foreign cells or tissues (called “non-self”). Similar types of glycoproteins and glycolipids are found on the surfaces of viruses and may change frequently, preventing immune cells from recognizing and attacking them. These carbohydrates on the exterior surface of the cell—the carbohydrate components of both glycoproteins and glycolipids—are collectively referred to as the glycocalyx (meaning “sugar coating”). The glycocalyx is highly hydrophilic and attracts large amounts of water to the surface of the cell. This aids in the interaction of the cell with its watery environment and in the cell’s ability to obtain substances dissolved in the water
Cellular membranes are somewhat fluid in nature. The fluidity of membranes is related to their composition - shorter, more unsaturated fatty acids make for membranes that retain fluidity at lower temperatures compared to longer, saturated fatty acids The Fluid Mosaic Model explains the fluidity of cellular membranes .
Fluid mosaic model two-dimensional fluids made up of lipid-bilayers interspersed with proteins. The fluidic nature of membranes is due to the constant rotational or lateral motion of both lipids and proteins
The lipid bilayer is not a static structure and is not rigid in nature. it has a fluidity that resembles olive oil and its about 100 times as viscous as water. phospholipids and many of the proteins actually move along a lateral direction of the membrane. This phenomenon is known as lateral diffusion.
Phospholipids tend to move along the membrane at a speed of 1 micrometer per second. Proteins however range in their movement; some are immobile while others are mobile. For instance rhodopsin, a photopigment found in retinal cells of the eye, function in part due to its constant movement along the membrane. Other proteins such as fibronectin are essentially immobile. This is because fibronectin, a peripheral glycoprotein, is anchored onto a transmembrane protein called integrin. Integrin itself is attached onto the actin filaments of the cytoskeleton. In addition, fibronectin is also attached to the collagen fibers of the extracellular matrix. Therefore all these attachment points make the fibronectin virtually immobile.
History The fluid mosaic model was first proposed by S.J. Singer and Garth L. Nicolson in 1972 to explain the structure of the plasma membrane. T he proportions of proteins, lipids, and carbohydrates in the plasma membrane vary with cell type. For example, myelin contains 18% protein and 76% lipid. The mitochondrial inner membrane contains 76% protein and 24% lipid.
The Asymmetry of the Lipid Bilayer Is Functionally Important The lipid compositions of the two monolayers of the lipid bilayer in many membranes are strikingly different. In the human red blood cell membrane, for example, almost all of the lipid molecules that have choline—(CH 3 ) 3 N + CH 2 CH 2 OH—in their head group (phosphatidylcholine and sphingomyelin) are in the outer monolayer , whereas almost all of the phospholipid molecules that contain a terminal primary amino group (phosphatidylethanolamine and phosphatidylserine) are in the inner monolayer Because the negatively charged phosphatidylserine is located in the inner monolayer, there is a significant difference in charge between the two halves of the bilayer .
Lipid asymmetry is functionally important. Many cytosolic proteins bind to specific lipid head groups found in the cytosolic monolayer of the lipid bilayer. The enzyme protein kinase C (PKC ), for example, is activated in response to various extracellular signals. It binds to the cytosolic face of the plasma membrane, where phosphatidylserine is concentrated, and requires this negatively charged phospholipid for its activity. In other cases, the lipid head group must first be modified so that protein binding sites are created at a particular time and place. Phosphatidylinositol, for instance, is a minor phospholipid that is concentrated in the cytosolic monolayer of cell membranes. A variety of lipid kinases can add phosphate groups at distinct positions in the inositol ring. The phosphorylated inositol phospholipids then act as binding sites that recruit specific proteins from the cytosol to the membrane. An important example of a lipid kinase is phosphatidylinositol kinase (PI 3-kinase) , which is activated in response to extracellular signals and helps to recruit specific intracellular signalling proteins to the cytosolic face of the plasma membrane
phosphatidylserine and phosphatidylinositol have a net negative charge at physiologic pH. Being present predominately in the inner leaflet, these two lipids generate a significant difference in charge between the two leaflets of the lipid bilayer. membrane lipid asymmetry is important for signal transduction . Extracellular expression of phosphatidyl serine targets the cell for engulfment by macrophages and is widely used as a diagnostic marker for apoptosis . Maintaining membrane lipid asymmetry is therefore highly important for cell homeostasis.
The orderly movement of polar/ionic compounds is critical for the cell to be able to get food for energy; Export materials ; maintain osmotic balance ; create gradients for secondary transport; Provide electromotive force for nerve signalling; store energy in electrochemical gradients for ATP production ( oxidative phosphorylation)