BIOLOGICAL CELL MEMBRANE OF THE CELLS PRESENT IN LIFE

A lecture on biological membrane of cells

1. BIOLOGICAL MEMBRANE LECTURER : PROF MRS J.E IKEKPEAZU

2. Introduction Membranes are highly viscous, pliable structures that define the borders of the cell and keep the cell functional . They are described as a continuous sheet of lipid molecules arranged as a molecular bilayer (lipid bilayer), 4-5mm thick. They form closed compartments around cellular protoplasm to separate one cell from another and therefore permit cellular individuality. Membranes also form specialized compartments within the cell (intracellular membranes) which help to form morphologically distinguishable structures (organelles) such as the mitochondria, ER, sarcoplasmic reticulum, Golgi complexes, secretory granules, lysosomes, and the nuclear membrane. They localize enzymes, function as integral elements in excitation-response coupling, and provide sites of energy transduction, such as in oxidative phosphorylation.

3. They are selectively permeable, allowing certain substances to move freely in and out the cell, while some others cannot move freely but require the use of some specialized structure/ transport mechanisms or even energy . The selective permeabilities are provided mainly by channels and pumps for ions and substrates. The plasma membrane exchanges materials with the extracellular environment by exocytosis and endocytosis. Special areas of membrane structure called the gap junctions exist through which adjacent cells exchange material . The plasma membranes therefore play key roles in cell-cell interactions and in transmembrane signaling.

4. SOME IMPORTANT FACTS TO NOTE ABOUT THE CELL MEMBRANE: The individual lipids and proteins of the plasma membrane are not covalently linked (see later ), The entire structure is therefore flexible, allowing changes in the shape and size of the cell . As the cell grows, newly made lipid and protein molecules are inserted into its plasma membrane . Cell division produces two cells, each with its own membrane.

5. Growth and cell division occurs without loss of membrane integrity. In addition to plasma membrane (external cell membrane); eukaryotic cells also contain internal membranes that form the boundaries of organelles such as mitochondria, peroxisomes , and lysosomes . The external and internal membranes have essential features in common.

6. CHEMICAL COMPOSITION OF MEMBRANES Lipids and proteins are the two major components of cell membrane . Membranes also contain a small amount of various polysaccharides as glycoprotein and glycolipid , but not free carbohydrate. The three major kinds of membrane lipid are phospholipids, glycolipids and cholesterol.

7. lipid composition varies between membranes. Tissue and various cell membranes have a distinctive lipid composition. The membranes of a specific tissue ( e.g liver) in different species contain very similar classes of lipids. The plasma membrane exhibits the greatest variation in percentage composition because the cholesterol content is affected by the nutritional state of the animal.

8. Myelin membrane of neuronal axons is rich in sphingolipids such as sphingomyelin . Intracellular membranes – for example, endoplasmic reticulum contain primarily glycerophospholipids and little sphingolipids . The membrane lipid composition of mitochondria, nuclei, and rough endoplasmic reticulum is similar, with that of Golgi complex being somewhere between that of other intracellular membranes and the plasma membrane.

9. The amount of cardiolipin is high in the inner mitochondrial membrane and low in the outer membrane, with essentially non in other membranes. The choline -containing lipids , phosphatidylcholine and sphingomyelin are most common, followed by phosphatidylethanolamine . The constancy of composition of various membranes suggests a relationship between their lipids and the specific functions of those membranes.

10. Membrane proteins Membrane proteins are classified based on the ease of removal of the protein from the membrane Integral (or intrinsic) membrane proteins. They span the lipid bilayer and are in contact with the aqueous environment on both sides. Integral proteins contain sequences rich in hydrophobic amino acid which interact with the hydrophobic hydrocarbons of the lipids, thereby stabilizing the protein lipid complex.

11. The removal of integral membrane proteins thus requires disruption of the membrane by detergent or organic solvents and when isolated, usually contain tightly bound lipid. Many integral proteins are glycoproteins . Integral proteins are embedded and are asymmetric in the membrane.

12. They have a defined , rather than a random orientation. The orientation of proteins is determined by their primary structure. Just like non-membrane proteins, they contain specific domains for ligand binding; for catalytic or transport activity, and for attachment of carbohydrate or lipid. For some proteins, the amino and carboxyl termini are both on one side of the membrane, whereas for others they are on opposite sides, frequently with the carboxyl terminus on the cytoplasmic side . Some integral proteins form multiple subunits structures in order to carry out their function (see diagram).

13. Interactions of membrane proteins with the lipid bilayer .

14. PERIPHERAL (EXTRINSIC) MEMBRANE PROTEINS They are located on the surface of membranes and can be easily removed without disrupting the lipid bilayer . Some bind to integral membrane proteins. Negatively charged phospholipids of membranes interact with positively charged regions of proteins and produce electrostatic binding. In some cases Ca 2+ mediates the binding.

15. Several peripheral proteins have short sequences of hydrophobic aminoacids at one end that serve as a membrane anchor, eg . Cytochrome b5 is attached to the endoplasmic reticulum by such an anchor at the carboxyl terminus. Other peripheral membrane proteins have specific conserved domain that binds non-covalently to the inositol 3 phosphate head group of phosphatidylinositol fixed in the membrane.

16. Interactions of membrane proteins with the lipid bilayer .

17. Diagram illustrates the multiple types of binding of proteins in or to the lipid bilayer (a) a single transmembrane segment (b) multiple transmembrane segments (c) bound to an integral protein (d) bound electrostatically to the lipid bilayer (e) attached by a short terminal hydrophobic sequence of amino acids; and (f) noncovalent binding to a phosphatidy linositol (PI) in the membrane.

18. The peripheral proteins are released by treatment with salt solutions of different ionic strength, extremes of pH or cleavage of covalently bound lipid that serves to attach the protein to the membrane .

19. LIPID ANCHORED PROTEINS Some peripheral membrane proteins as mentioned earlier are attached to the membrane by covalently linked lipid. The lipid is inserted into the lipid membrane, anchoring the protein to the membrane e.g GPI ANCHOR phosphatidylinositol is attached to a glycan (consisting of ethanolamine, phosphate, mannose, mannose, mannose, and glucosamine). The glycan is covalently bound to the carboxyl terminus of a protein by ethanolamine and the glucosamine is linked covalently to phosphatidylinositol . The fatty acyl groups of phosphatidylinositol are then inserted into the lipid membrane, thus anchoring the protein. This form of attachment is referred to as a glycosyl phosphatidylinositol (GPI) anchor. See below

20. GPI ANCHOR

21. Note : This type of anchoring is important because release and reattachment of the protein to the anchor can be controlled, thereby allowing protein regulation of the activity of the protein.

22. membrane carbohydrate Carbohydrates are present in membranes as oligosaccharide, covalently attached to proteins ( glycoproteins ) and to lipids ( glycolipids ). The sugars in the oligosaccharides include glucose, galactose , mannose, fucose , N- acetylgalactosamine , N- acetylglucosamine and N- acetylneuraminic acid ( sialic acid). The carbohydrate is on the extracellular surface of plasma membrane and the luminal surface of endoplasmic reticulum. There is little or no free carbohydrate in membrane .(see diagram)

23. Roles of membrane proteins Membrane proteins have a variety of functions. They serve as Mediators of transmembrane movement of charged and uncharged molecules Receptors for the binding of hormones and growth factors Enzymes involved in transduction of signals Molecular pumps Some integral membrane proteins have a structural role to maintain the shape of the cell Roles of protein bound carbohydrates of membrane include (1)Cell-cell recognition (2) adhesion and (3) receptor-action

24. FLUID MOSAIC MODEL OF MEMBRANE STRUCTURE The fluid mosaic model, now widely accepted, was proposed by S. J. Singer and G.L Nicholson in the early 1970s. This model of membrane structure was likened to icebergs (membrane proteins) floating in a sea of predominantly phospholipid molecules. The fluid mosaic model therefore describes the structure of the plasma membrane as a mosaic of components —including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.

25. The membrane consists of a bimolecular layer of lipid with proteins inserted in it or bound to either surface, Those embedded in either the outer or inner leaflet of the lipid bilayer , that is, Loosely bound to the outer or inner surface of the membrane are the peripheral proteins (see earlier). Integral membrane proteins are firmly embedded in the lipid layers and are also called transmembrane proteins

26. Many of the proteins and lipids have externally exposed oligosaccharide chains. Both lipids and proteins are considered to diffuse laterally in the membrane. Their (lipids and proteins) distribution in cellular membranes are thus not homogenous. Many of the properties of cellular membrane in this regard include, fluidity, and flexibility that permits change of shape and form, ability to self seal and impermiability . Membranes are asymmetric structures.

27. Although membrane models suggest that some proteins are randomly distributed throughout or on the membrane, there is a high degree of functional organisation with definite restrictions on the localization of some proteins.

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