1. Introduction
An essential feature of every cell is the presence of membranes that define the boundaries of the cell and delineate its various internal compartments. We are going to look at membrane structure and function in greater detail by examining the molecular structure of membranes and explore the multiple roles that membranes play in the life of the cell.
2. Functions of Membranes
(1) Delineation and Compartmentalization. To delineate the boundaries of the cell and its compartments. The interior of the cell must be physically separated from the surrounding environment not only to keep desirable substances in the cell but to keep undesirable substances out. Membranes serve this purpose well because the hydrophobic interior of the membrane is an effective barrier for hydrophilic molecules and ions. For the cell as a whole, the plasma membrane is the permeability barrier. In addition to the plasma membrane, various intercellular membranes serve to compartmentalize function within eukaryotic cells.
(2) Localization and Organization of Function. The molecules and structures responsible for specific functions are either embedded in or localized on membranes. The localization of specific functions to membranes is exemplified by roles of the inner membrane of the mitochondria and the thylakoid membranes of the chloroplast in the process of cellular respiration and photosynthesis. Membrane associations are also evident for other cellular components including the many enzymes known to be localized in or on the membrane of organelles such as the ER, GA, lysosomes and peroxisomes. Thus, membranes also function as sites for enzymatic reactions.
(3) Regulation of Transport. To provide for and regulate the movement of substances into and out of cells and their organelles. Nutrients, ions, gases, water and other substances are taken up by the cell and various products and wastes must be removed.
(4) Detection and Transmission of Signals. Cells receive information from their environment, usually in the form of electrical or chemical signals that impinge upon the outer surface of the cell. The various hormones in the circulatory system, growth-promoting substances and neurotransmitters are examples of such signals. These signals can cause changes in either the nature or the rate of cellular activities. The information that impinges on the cell initiates new patterns or cycles of activities such as cell division or differentiation. The plasma membrane plays a key role in signal transduction.
(5) Cell-to-Cell Communication. Membranes also provide a means of communication between adjacent cells. Many cells in multi-cellular organisms are in contact with one another via direct cytoplasmic connections. This cell-to-cell communication is provided by intercellular junctions in animal cells and by plasmodesmata in plant cells.
3. Brief Historical Perspective
Overton discovered that membranes are made of lipids. In general, lipid soluble materials penetrate readily into cells by dissolving in the lipid element that made up the membrane whereas water-soluble substances did not.
Langmuir discovered that lipid in water form a monolayer membrane which shows the amphipatic mature of lipids.
Gorter and Grendel discovered that cell membranes actually made up of phospholipids bilayer. The evidence for this is that the phospholipids content of membranes isolated from red blood cells were just enough to cover the cell with two layers.
Davson and Danielli discovered that membranes are made up of phospholipids bilayer sandwiched between 2 layers of globular proteins. They proposed that membranes exhibit selective permeability, the ability to distinguish between molecules of different sizes and solubilities and between ions of different charges.
Robertson discovered that the membrane is trilaminar i.e. made of two electron dense bands separated by an unstained layer through TEM. The protein molecules extended into a layer one amino acid in thickness. At intervals, polar pores coated by protein perforate the membrane. The overall thickness of the membrane is about 7.5 nm.
4. The Fluid Mosaic Model
The membrane is a mosaic of protein molecules floating in a fluid phospholipids bilayer. The thickness of the membrane is approximately 6-10 nm. It is asymmetrical. The two lipid layers may differ in lipid and protein composition. Carbohydrates are restricted to the membrane’s exterior. The evidence are obtained through EM and freeze fracture techniques. When halves of the fractured membrane is viewed with the EM, the interior of the bilayer appears cobblestoned, with protein particles interspersed in a smooth matrix. This provided proof that proteins are embedded in the phospholipids bilayer of the membrane.
4.1 Common Features of Membranes
Membranes are sheet-like structures, only a few molecules thick that form closed boundaries between different compartments. Membranes consist of mainly lipids and proteins. They also contain carbohydrates that are linked to lipids and proteins.
Membrane lipids are relatively small molecules that have both a hydrophilic and hydrophobic moiety. These lipids spontaneously form closed bimolecular sheets in aqueous media these lipid bilayers are barriers to the flow of polar molecules. Specific proteins mediate distinctive functions of membranes. Proteins serve as pumps, channels, receptors, energy transducers and enzymes. Membrane proteins are embedded in lipid bilayers, which create suitable environments for their action.
Membranes are non-covalent assemblies. The constituent protein and lipid molecules are held together by non-covalent interactions, which are cooperative. Membranes are asymmetric. The two faces of biological membranes always differ from each other.
Membranes are fluid structures. Lipid molecules diffuse rapidly in the plane of the membrane, as do proteins, unless they are anchored by specific interactions. In contrast, they do not rotate across the membrane. Membranes can be regarded as two-dimensional solutions of oriented proteins and lipids. Most membranes are electrically polarized, with the inside negative (about -60 mV). Membrane potential plays a key role in transport, energy conversion and transmission of nerve impulses.
4.2 Chemical Composition of Membranes
4.2.1 Membrane Lipids
4.2.1.1 Types of Membrane Lipids
Examples are phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, cardiolipin, phosphatidyl inositol, sphingolipids, glycolipids, cholesterol.
4.2.1.2 Structure of Membrane Lipids
Amphipatic i.e. polar groups (heads) are charged and have affinity for water molecules (hydrophilic); non-polar groups (hydrocarbon tails / fatty acid chains) do not mix with water (hydrophobic). Unsaturated phospholipids have kinks or sharp bends un their fatty acid tails. Because of the non-linearity of their side chains, fatty acids with double bonds prevent close packing in the membranes. Phospholipid molecules are responsible for the formation of bilayers in water. The long hydrocarbon chains of the fatty acids form an effective hydrophobic barrier to the diffusion of polar solutes. Thickness of the membranes is dictated by the chain length of the fatty acids.
4.2.1.3 Membrane Mobility
The phospholipids molecules are held together by hydrophobic interactions. They are free to move laterally within the membrane. But rarely flip transversely across the membrane because the hydrophilic parts would have to cross the membrane’s hydrophobic core.
Unsaturated hydrocarbon tails have kinks, thus preventing the hydrocarbon chains from packing together, enhancing membrane fluidity. Membrane lipids with saturated fatty acids pack together tightly, thereby optimizing their van der Waals interactions. Cholesterol contributes to membrane fluidity by hindering the packing together of phospholipids.
4.2.1.4 Membrane Fluidity & Temperature
Membrane fluidity changes with temperature, decreasing as the temperature drops and increasing as it rises. Every lipid bilayer has a characteristic transition temperature at which it gels when cooled and becomes fluid again when warmed. This change in state of the membrane is called phase transition. Phase transition is a rearrangement of hydrocarbon chains within the bilayers brought about by changes in temperature. Fluidity of a membrane depends on kinds of lipids present.
The three most important aspects of lipid composition that affect membrane fluidity are as follows: (1) length of fatty acids, (2) degree of unsaturation of side chains and (3) for animal membranes, the amount of cholesterol present.
At low temperatures, the hydrocarbon chains are tightly packed, thus optimizing their van der Waals interactions. Thus their motion is restricted. The bilayer approximates a semisolid gel.
At high temperatures, both the space separating adjacent phospholipids molecules and the motion of hydrocarbon chains increase. The increased freedom of phospholipids above the phase transition includes rotation of entire molecules around their long axis, flexing of hydrocarbon chains and the lateral movement or diffusion of individual molecules through the bilayer. Under these conditions the bilayer interior is fluid. Generally, the longer the hydrocarbon chains, the higher the phase transition temperature. Double bonds introduce kinks or bends in the hydrocarbon chains which interferes with the tight packing of the phospholipids of the bilayer, thus allowing the bilayer to remain fluid at lower temperatures and thus decreasing melting temperature.
Mixtures of phospholipids broaden the temperature range of the transition phase. Cells living at low temperature have higher proportions of unsaturated fatty acids in their membranes than do cells at higher temperature. Winter wheat increases concentration of membrane unsaturated phospholipids and some hibernating animals enrich membranes with cholesterol.
4.2.2 Cholesterol
4.2.2.1 Occurance
Occurs in the phospholipids bilayer but to a minor extent in intracellular membrane. Absent from inner membrane of mitochondria and chloroplast as well as membranes of bacteria and plant cells. Without cholesterol, a cell would need a cell wall. It is a common component of animal cell membrane.
4.2.2.2 Structure
It is a steroid. It lines up between the phospholipids molecules of a bilayer half, with its long axis parallel to the hydrocarbon chains of the phospholipids, thus, it interferes with the tight packing of hydrocarbon chains which is necessary for traction to the gel phase.
4.2.2.3 Effects of Cholesterol on Membrane Fluidity
Cholesterol molecules are usually found in both layers of the plasma membrane, but a given molecule is localized to one of the two layers.
(1) The intercalation of cholesterol molecules into the lipid monolayer results in reduced membrane fluidity at higher temperatures.
(2) Cholesterol also effectively prevents the hydrocarbon chains of phospholipids from aggregating as temperature is decreased thereby reducing the tendency of membranes to “freeze” upon cooling. Thus, cholesterol acts as a bilayer “antifreeze” and keeps the bilayer fluid at lower temperatures.
(3) Cholesterol also decreases the permeability of a lipid bilayer to ions and small polar molecules. It does so by filling in spaces between hydrocarbon chains if the membrane phospholipids, thereby plugging small channels through which ions and small molecules might otherwise pass. In general, a lipid bilayer containing cholesterol is less permeable to ions and small molecules than a bilayer lacking cholesterol.
(4) Cholesterol enhances both the flexibility and mechanical stability of the bilayer. It immobilizes the first few hydrocarbon groups of the phospholipid molecules, making the bilayer less deformable.
4.2.3 Protein
4.2.3.1 Structure
Majority of proteins exist in globular form as a dispersed unit that float or are embedded individually or in groups in a lipid bilayer. Proteins provide the mosaic part of the model. Carbohydrates associated with the hydrophilic region facing the cell’s surroundings are believed to play a role in maintaining the orientation of the protein within the membrane. Proteins drift more slowly than lipids in the bilayer. The fast that proteins drift laterally was established by fusing a human and mouse cell.
4.2.3.2 Classification by Structure
Integral proteins are deeply embedded in the hydrophobic membrane interior of the lipid bilayer. They may be unilateral reaching only the monolayer of the membrane or transmembrane that spans the whole lipid bilayer and contains an outer region that is hydrophilic as well as a central region that is hydrophobic. They are held in place by extensive hydrophobic interactions with the hydrocarbon portions of the membrane phospholipids. Integral proteins are usually insoluble in aqueous media. They are released from the membrane only by use of detergents or non-polar solvents.
Peripheral proteins are not embedded but are loosely attached to the membrane’s surface. They may be attached to integral proteins. On the cytoplasmic side, they may be held by network proteins and cannot move far. They are rich in amino acids with hydrophilic side chains that permit interactions with the surrounding water and polar surface of the lipid bilayer. These extrinsic proteins are usually soluble in aqueous media. They can be removed by relatively mild treatments such as adjustments if the ionic strength or pH of the suspending medium.
4.2.3.3 Functions of Proteins in Membranes
(1) Anchoring proteins. These proteins may attach the cell membrane to other structures and stabilize its position. Inside the cell, they are bound to the cytoskeleton, a network of supporting filaments within the cytoplasm. Outside the cell, they may attach the cell to extra-cellular protein fibers or to another cell.
(2) Recognition Proteins. The cells of the immune system recognize other cells as normal or abnormal on the basis of the presence or absence of characteristic recognition proteins. Many important recognition proteins are glycoproteins.
(3) Enzymes. They may be integral of peripheral proteins and catalyze reactions in the extra-cellular fluid or within the cytosol depending on the location of the protein and its active site. Dipeptides are broken down to amino acids by enzymes on the exposed membranes of cells lining the intestinal tract.
(4) Receptor Proteins. They are sensitive to presence of specific extra-cellular molecules called ligands. A receptor protein exposed to an appropriate ligand will bind to it and this may trigger changes in the activity of the cell. Cell membranes differ in the type and number of receptor proteins and it is these differences that account for their differing sensitivities to hormomes and solutes.
(5) Carrier Proteins. They bind solutes and transport them across the cell membrane. The transport process involves a change in the shape of the carrier protein (the shape changes when solute binding occurs and returns to original form when the solute is released). Carrier proteins may or may not require ATP as an energy source.
(6) Channels. Some integral proteins contain a central pore, or channel, that forms a passageway that permits the movement of water and small solutes across the cell membrane. Ions do not dissolve in lipids and they cannot cross the bilayer. Thus, ions and small water soluble materials can cross the membrane only by passing through channels. Leak channels permit water and ion movement at all times. Gated channels can open and close to regulate ion passage.
4.2.4 Carbohydrates
4.2.4.1 Structure
Carbohydrates exist as short, branched chains of sugars (oligosaccharides) about 15 monomers long and are covalently bound to external peripheral proteins or polar ends of phospholipids in the outer lipid layer forming glycolipids.
4.2.4.2 Functions of Carbohydrates in Membranes
They contribute to membrane stability. Because they are highly hydrophilic, the sugars help to orient the glycoproteins and glycolipids in the membrane so that they are kept in contact with the external aqueous environment and are unlikely either to rotate toward the interior or diffuse transversely.
They are important as components for the recognition sites of membrane receptors such as those involved in (1) binding extra-cellular signal molecules in antibody-antigen reactions, (2) intercellular adhesion to form tissues and (3) cell-cell recognition.
