What is Cell Membrane?
Cell membrane is also known as Plasma Membrane, Cytoplasmic Membrane and historically referred to as the Plasmalemma. Plasma membrane encloses every type of cell, both prokaryotic and eukaryotic cell. The term cell membrane was coined by C. Nageli and C. Cramer in 1855 and the term plasmalemma has been given by J.Q. Plowe in 1931.
All biological membrane including plasma membrane and internal membranes of eukaryotic cell (i.e., membranes bounding endoplasmic reticulum or ER, nucleus, mitochondria, chloroplast, Golgi apparatus, lysosomes, peroxisomes, etc.) are similar in structure (i.e., fluid-mosaic) and selective permeability but differing in other functions.
Cell membrane constituent as the essential physiological barrier at the surface to the cells. Also cell have different environment from the milieu which surround them. This difference is maintained by the cell membrane which is responsible for the iron and fluid transport. The absorption of cell molecules and the uptake of macromolecules and particular material by endocytosis.
Cell membrane also interact with the surrounding extracellular matrix molecules and with the underlaying intracellular cytoskeletal framework and its associated proteins, which regulate the cell shape and respond to the external and internal stimuli.
Chemical composition of cell membrane:
Chemically, plasma membrane and other membranes of different organelles are found to contain proteins, lipids and carbohydrates, but in different ratios. For example, in the cell membrane of the human blood cells protein present 52%, lipid 40 % and carbohydrates 8%.
Four major classes of lipids are commonly present in the cell membrane and other membranes: phospholipids (most abundant), sphingolipids, glycolipids and sterols (e.g., cholesterol). All of them are amphipathic molecules, possessing both hydrophilic and hydrophobic domains.
The relative proportions of these lipids vary in different membranes. Phospholipids may be acidic phospholipids (20%) such as sphingomyelin or neutral phospholipids (80%) such as phosphatidyl choline, phosphatidylserine, etc.
Many membranes contain cholesterol. Cholesterol is especially abundant in the plasma membrane of mammalian cells and absent from prokaryotic cells. Cardiolipin (diphosphatidyl glycerol) is restricted to the inner mitochondrial membrane.
The amount and types of proteins in the membranes are highly variable: in the myelin membranes which serve mainly to insulate nerve cell axons, less than 25% of the membrane mass is protein, whereas, in the membranes involved in energy transduction (such as internal membranes of mitochondria and chloroplasts), approximately 75% is protein. Cell membrane contains about 50% protein.
According to their position in the cell membrane, the proteins fall into two main types: integral or intrinsic proteins and peripheral or extrinsic proteins, both of which may be either ectoproteins, lying or exposing to external or extra cytoplasmic surface of the cell membrane or endoproteins, lying or sticking out at the inner or cytoplasmic surface of the cell membrane.
The intrinsic proteins tend to associate firmly with the membrane, while the extrinsic proteins have a weaker association and are bound to lipids of membrane by electrostatic interaction. On the basis of their functions, proteins of cell membrane can also be classified into three main types: structural proteins, enzymes and transport proteins (permeases or carriers). Some of them may act as antigens, receptor molecules (e.g., insulin binding sites of liver plasma membrane), regulatory molecules and so on.
Structural proteins are extremely lipophilic and form the main bulk (i.e., backbone) of the plasma membrane. Enzymes of cell membrane are either ectoenzymes or endoenzymes and are of about 30 types. Transport proteins transport specific substances across the cell membrane and other cellular membranes.
Carbohydrates are present only in the cell membrane. They are present as short, unbranched or branched chains of sugars (oligosaccharides) attached either to exterior ectoproteins (forming glycoproteins) or to the polar ends of phospholipids at the external surface of the cell membrane (forming glycolipids).
No carbohydrate is located at the cytoplasmic or inner surface of the cell membrane. All types of oligosaccharides of the cell membrane are formed by various combinations of six principal sugars (all of which are glucose-derivatives): D-galactose, D-mannose, L-fucose, N-acetylneuraminic acid (also called sialic acid), N-acetyl-D-glucosamine and N-acetyl-D-galactosamine.
Structure of Cell Membrane
Like all other cellular membranes, the plasma membrane consists of both lipids and proteins. The fundamental structure of the membrane is the phospholipid bilayer, which forms a stable barrier between two aqueous compartments. In the case of the plasma membrane, these compartments are the inside and the outside of the cell. Proteins embedded within the phospholipid bilayer carry out the specific functions of the plasma membrane, including selective transport of molecules and cell-cell recognition.
Fluid mosaic model:
The existence of the plasma membrane of the cell was difficult to prove by direct examination before 1930’s (when electron microscopy was invented) because of technological limitations. The membrane is beyond the resolution of the light microscope, rendering a morphological approach of its study quite unfeasible with this instrument. Thus, most of the experimental approaches have been provided by only indirect evidences of the existence of such a membrane around the cells.
S.J.Singer and G.L.Nicolson (1972) suggested the widely accepted fluid mosaic model of biological membranes. According to this model, the plasma membrane contains a bimolecular lipid layer, both surfaces of which are interrupted by protein molecules.
Proteins occur in the form of globular molecules and they are dotted about here and there in a mosaic pattern. Some proteins are attached at the polar surface of the lipid (i.e., the extrinsic proteins); while others (i.e., integral proteins) either partially penetrate the bilayer or span the membrane entirely to stick out on both sides (called transmembrane proteins).
Further, the peripheral proteins and those parts of the integral proteins that stick on the outer surface (i.e., ectoproteins) frequently contain chains of sugar or oligosaccharides (i.e., they are glycoproteins). Likewise, some lipids of outer surface are glycolipids.
The fluid-mosaic membrane is thought to be a far less rigid than was originally supposed. In fact, experiments on its viscosity suggest that it is of a fluid consistency rather like the oil, and that there is a considerable sideways movement of the lipid and protein molecules within it.
On account of its fluidity and the mosaic arrangement of protein molecules, this model of membrane structure is known as the “fluid mosaic model” (i.e., it describes both properties and organization of the membrane).
The fluid mosaic model is found to be applied to all biological membranes in general, and it is seen as a dynamic, ever-changing structure. The proteins are present not to give it strength, but to serve as enzymes catalyzing chemical reactions within the membrane and as pumps moving things across it.
Membrane lipid and their function
A). Types of movements of lipid molecules.
Lipid molecules very rarely migrate from one lipid monolayer to another monolayer of lipid bimolecular layer. Such a type of movement is called flip-flop or trans bilayer movement and occurs once a month for any individual lipid molecule.
However, in membranes where lipids are actively synthesized, such as smooth ER, there is a rapid flip-flop of specific lipid molecules across the bilayer and there are present certain membrane-bound enzymes, called phospholipid translocators (e.g., flippase) to catalyze this activity (Bishop and Bell, 1988).
On the other hand, lipid molecules readily exchange places with their neighbors within a monolayer (~ 107 times a second). This results in their rapid lateral diffusion. Individual lipid molecules rotate very rapidly about their long axes and their hydrocarbon chains are flexible, the greatest degree of flexion occurring near the centre of the bilayer and the smallest adjacent to the polar head groups.
B). Role of unsaturated fats in increasing membrane fluidity.
A synthetic bilayer made from a single type of phospholipid changes from a liquid state to a rigid crystalline or gel (viscous) state at a characteristic freezing point. This change of state is called a phase transition and the temperature at which it occurs becomes lower if the hydrocarbon chains are short or have double bonds.
Double bonds in unsaturated hydrocarbon chains tend to increase the fluidity of a phospholipid bilayer by making it more difficult to pack the chains together. Thus, to maintain fluidity of the membrane, cells of organisms living at low temperatures have high proportions of unsaturated fatty acids in their membranes, then do cells at higher temperatures.
In fact, certain membrane transport processes and enzyme activities are found to cease when the lipid bilayer’s viscosity increases beyond a threshold level. In contrast, if lipid bilayer’s fluidity is increased, the membrane’s receptors for the hormone are withdrawn from the cell surface, thereby hampering hormone action (see Sheeler and Bianchi, 1987).
C). Role of cholesterol in maintaining fluidity of membrane.
Eukaryotic plasma membranes are found to contain a large amount of cholesterol; up to one molecule for every phospholipid molecule. Cholesterol molecules orient themselves in the lipid bilayer in such a way that their hydroxyl groups remain close to polar head groups of the phospholipids, their rigid plate-like steroid rings interact with and partly immobilize those regions of hydrocarbon chains that are closest to the polar head groups, leaving the rest of the chain flexible.
Cholesterol inhibits phase transition by preventing hydrocarbon chains from coming together and crystallizing. Cholesterol also tends to decrease the permeability of lipid bilayers to small water-soluble molecules and is thought to enhance both the flexibility and the mechanical stability of the bilayer.
Both lipid and protein molecules have irregular distribution in both monolayers of the lipid bilayer, this is called membrane asymmetry.
A). Phospholipid asymmetry in cell membrane.
The lipid composition and state of fluidity of two halves of the lipid bilayer are found to be strikingly different. For example, in human erythrocyte’s plasma membrane, outer half contains those phospholipids which have more saturated fatty acid chains, and inner half contains those phospholipids which contain terminal amino groups and less saturated fatty acid chains.
As a result, inner monolayer is more fluid than the outer lipid monolayer. Such a phospholipid asymmetry is generated in smooth ER. The asymmetry of glycolipids such as galactocerebroside, ganglioside, etc., in myelin sheath of nerves (i.e., they are found only in the outer half of lipid bilayer) is found to be originated in lumen of Golgi apparatus. The specific role of lipid asymmetry of the membrane is still not clear.
B).Protein asymmetry in cell membrane.
The outer and inner sides of the plasma membrane and other membranes do not contain either the same types or equal amounts of the various peripheral and integral proteins, e.g., erythrocyte’s plasma membrane.
Proteins of plasma membrane of erythrocytes.
When the extracted proteins of the plasma membrane of human erythrocytes (RBC) are studied by SDS polyacrylamide-gel electrophoresis (SDS = sodium dodecyl sulphate; a detergent), approximately 15 major protein bands are detected, varying in molecular weight from 15,000 to 25,000. Most of these proteins are found to be peripheral proteins of cytosolic face of the plasma membrane.
Motility of Membrane Molecules
In the fluid mosaic plasma membrane, there is not complete and independent freedom of movement for its different component molecules. The mobility of some part of lipid molecules is constrained since that remains tightly bound to some of the integral membrane proteins.
For example, the mobility of lipid molecules surrounding cytochrome oxidase (an enzyme involved in the synthesis of ATP) are immobilized by the enzyme and makes boundary lipid layer. The immobilized boundary lipid makes 30 per cent of membrane lipid in the mitochondrial membrane.
In contrast to lipids, the mobility and distribution of protein molecules in the membrane is controlled by various ways:
- Certain proteins of the membrane are constrained by protein-protein interactions to form specialized ordered regions, representing 2 to 20 percent of the membrane of a system, e.g., gap junctions, synapsis of neurons, and plaques of halobacteria.
- Certain peripheral proteins (endoproteins) may form a bridge-like lattice work between integral proteins and restrict their lateral mobility, e.g., spectrin-ankyrin-actin cytoskeletal meshwork provides rigidity to the membrane of human erythrocytes and does not permit the clustering or capping of integral proteins when the appropriate antibodies or lectins are added.
- In nucleated eukaryotic cells, the mobility of the peripheral endoproteins and integral proteins is restrained by their attachment to the ectoplasmic cytoskeleton. The cytoskeleton is extensive, including myosin filaments, actin filaments, and microtubules.
Rearrangement of cytoskeletal components just below the cell surface manifests in the distribution of integral membrane proteins and also in the cellular motions, endocytosis and exocytosis. The inter-cellular space.
In the tissues of multicellular animals, the plasma membranes of two adjacent cells usually remain separated by a space of 10 to 150 Aº wide. This inter-cellular space is uniform and contains a material of low electron density which can be considered as a cementing substance. This substance is found to be a mucopolysaccharide
The function of Cell Membrane
The plasma membrane acts as a thin barrier that separates the intracellular fluid of the cytoplasm from the extra-cellular fluid in which the cell lives. In the case of unicellular organisms (Protophyta and Protozoa) the extra-cellular fluid may be fresh or marine water, while in multicellular organisms the extra-cellular fluid may be blood, lymph, or interstitial fluid.
Though the plasma membrane is a limiting barrier around the cell but it performs various important physiological functions which are as follows:
The plasma membrane is a thin, elastic membrane around the cell which usually allows the movement of small ions and molecules of various substances through it. This nature of the plasma membrane is termed permeability.
According to permeability following types of the plasma membranes have been recognized:
- Impermeable plasma membranes. The plasma membrane of the unfertilized eggs of certain fishes allows nothing to pass through it except the gases. Such plasma membranes can be termed as impermeable plasma membranes.
- Semi-permeable plasma membranes. The membranes which allow only water but no solute particle to pass through them are known as semi-permeable membranes. Such membranes have not so far been recognized in animal cells.
- Selectively permeable plasma membranes. The plasma membrane and other intracellular membranes are very selective in nature. Such membranes allow only certain selected ions and small molecules to pass through them.
- Dialysing plasma membranes. The plasma membranes of certain cells have certain extraneous coats around them. The basement membranes of endothelial cells are the best examples of extraneous coats. This type of plasma membrane having extraneous coats around it acts as a dialyzer. In these membranes, the water molecules and crystalloids are forced through them by the hydrostatic pressure forces.
Mode of Transport Across Plasma Membrane
The plasma membrane acts as a semipermeable barrier between the cell and the extracellular environment. This permeability must be highly selective if it is to ensure that essential molecules such as glucose, amino acids and lipids can readily enter the cell, that these molecules and metabolic intermediates remain in the cell, and that waste compounds leave the cell.
In short, the selective permeability of the plasma membrane allows the cell to maintain a constant internal environment (homeostasis). In consequence, in all types of cells there exists a difference in ionic concentration with the extracellular medium.
Similarly, the organelles within the cell often have a different internal environment from that of the surrounding cytosol and organelle membranes maintain this difference. For example, in lysosomes the concentration of protons (H+) is 100 to 1000 times that of the cytosol.
This gradient is maintained solely by the lysosomal membrane. Transport across the membrane may be passive or active. It may occur via the phospholipid bilayer or by the help of specific integral membrane proteins, called permeases or transport proteins.
It is a type of diffusion in which an ion or molecule crossing a membrane moves down its electrochemical or concentration gradient. No metabolic energy is consumed in passive transport. Passive transport is of following three types:
The plasma membrane is permeable to water molecules. The to and fro movement of water molecules through the plasma membrane occurs due to the differences in the concentration of the solute on either sides.
The process by which the water molecules pass through a membrane from a region of higher water concentration to the region of lower water concentration is known as osmosis. The process in which the water molecules enter into the cell is known as endosmosis, while the reverse process which involves the exit of the water molecules from the cell is known as exosmosis.
In plant cells due to excessive exosmosis the cytoplasm along with the plasma membrane shrinks away from the cell wall. This process is known as plasmolysis. A cell contains variety of solutes in it, for instance, the mammalian erythrocytes contain the ions of potassium (K+), calcium (Ca+), phosphate (PO4—), dissolved hemoglobin and many other substances.
If the erythrocyte is placed in a 0.9% solution of sodium chloride (NaCl), then it neither shrinks nor swells. In such case, because the intra-cellular and extracellular fluids contain same concentration and no osmosis takes place.
This type of extra-cellular solution or fluid is known as isotonic solution or fluid. If the concentration of NaCl solution is increased above 0.9% then the erythrocytes are shrinked due to excessive exosmosis.
The solutions which have higher concentrations of solutes than the intracellular fluids are known as hypertonic solutions. Further, if the concentration of NaCl solution decreases below 0.9% the erythrocytes will swell up due to endosmosis.
The extra-cellular solutions having less concentration of the solutes than the cytoplasm are known as hypotonic solutions. Due to endosmosis or exosmosis the water molecules come in or go out of the cell.
The amount of the water inside the cell causes a pressure known as hydrostatic pressure. The hydrostatic pressure which is caused by the osmosis is known as osmotic pressure. The plasma membrane maintains a balance between the osmotic pressure of the intra-cellular and inter-cellular fluids.
B). Simple diffusion.
In simple diffusion, transport across the membrane takes place unaided, i.e., molecules of gases such as oxygen and carbon dioxide and small molecules (e.g., ethanol) enter the cell by crossing the plasma membrane without the help of any permease.
During simple diffusion, a small molecule in aqueous solution dissolves into the phospholipid bilayer, crosses it and then dissolves into the aqueous solution on the opposite side. There is little specificity to the process.
The relative rate of diffusion of the molecule across the phospholipid bilayer will be proportional to the concentration gradient across the membrane.
C). Facilitated diffusion.
This is a special type of passive transport, in which ions or molecules cross the membrane rapidly because specific permeases in the membrane facilitate their crossing. Like the simple diffusion, facilitated diffusion does not require the metabolic energy and it occurs only in the direction of a concentration gradient.
Facilitated diffusion is characterized by the following special features:
- the rate of transport of the molecule across the membrane is far greater than would be expected from simple diffusion.
- This process is specific; each facilitated diffusion protein (called protein channel) transports only a single species of ion or molecule.
- There is a maximum rate of transport, i.e., when the concentration gradient of molecules across the membrane is low, an increase in concentration gradient results in a corresponding increase in the rate of transport.
Currently, it is believed that transport proteins form the channels through the membrane that permits certain ions or molecules to pass across the latter the simple diffusion, facilitated diffusion does not require the metabolic energy and it occurs only in the direction of a concentration gradient.
Active transport uses specific transport proteins, called pumps, which use metabolic energy (ATP) to move ions or molecules against their concentration gradient. For example, in both vertebrates and invertebrates, the concentration of sodium ion is about 10 to 20 times higher in the blood than within the cell.
The concentration of the potassium ion is the reverse, generally 20 to 40 times higher inside the cell. Such a low sodium concentration inside the cell is maintained by the sodium-potassium pump. There are different types of pumps for the different types of ions or molecules such as calcium pump, proton pump, etc.
A). Bulk transport by the plasma membrane.
Cells routinely import and export large molecules across the plasma membrane. Macromolecules are secreted out from the cell by exocytosis and are ingested into the cell from outside through phagocytosis and endocytosis.
It is also called emeiocytosis and cell vomiting. In all eukaryotic cells, secretory vesicles are continually carrying new plasma membrane and cellular secretions such as proteins, lipids and carbohydrates (e.g., cellulose) from the Golgi apparatus to the plasma membrane or to cell exterior by the process of exocytosis.
The proteins to be secreted are synthesized on the rough endoplasmic reticulum (RER). They pass into the lumen of the ER, glycosidated and are transported to the Golgi apparatus by ER-derived transport vesicles.
In the Golgi apparatus the proteins are modified, concentrated, further glycosidated, sorted and finally packaged into vesicles that pinch off from trans Golgi tubules and migrate to plasma membrane to fuse with it and release the secretion to cell’s exterior.
In contrast, small molecules to be secreted (e.g., histamine by the mast cells) are actively transported from the cytosol (where they are synthesized on the free ribosomes) into preformed vesicles, where they are complexed to specific macromolecules (e.g., a network of proteoglycans, in case of histamine; Lawson et al., 1975), so that, they can be stored at high concentration without generating an excessive osmotic gradient.
During exocytosis the vesicle membrane is incorporated into the plasma membrane. The amount of secretory vesicle membrane that is temporarily added to the plasma membrane can be enormous: in a pancreatic acinar cell discharging digestive enzymes, about 900 μm2 of vesicle membrane is inserted into the apical plasma membrane (whose area is only 30 μm3) when the cell is stimulated to secrete
In endocytosis, small regions of the plasma membrane fold inwards or invaginate, until it has formed new intracellular membrane limited vesicles. In eukaryotes, the following two types of endocytosis can occur: pinocytosis and receptor-mediated endocytosis.
Pinocytosis is the non-specific uptake of small droplets of extracellular fluid by endocytic vesicles or pinosomes, having diameter of about 0.1 μm to 0.2 μm. Any material dissolved in the extracellular fluid is internalized in proportion to its concentration in the fluid.
The process of pinocytosis was first of all observed by Edward in Amoeba and by Lewis (1931) in the cultured cells. The light microscopy has shown that in Amoeba tiny pinocytic channels are continually being formed at the cell surface by invagination of the plasma membrane.
From the inner end of each channel small vacuoles or pinosomes are pinched off, and these move towards the centre of the cell, where they fuse with primary lysosomes, to form food vacuoles. Ultimately, ingested contents are digested, small breakdown products such as sugars and amino acids diffuse to cytosol.
In this type of endocytosis, a specific receptor on the surface of the plasma membrane “recognizes” an extracellular macromolecule and binds with it. The substance bound with the receptor is called the ligand.
Examples of ligands may include viruses, small proteins (e.g., insulin, vitellogenin, immunoglobin, transferrin, etc.), vitamin B12, cholesterol containing LDL or low-density lipoprotein, oligosaccharide, etc. The region of plasma membrane containing the receptor-ligand complex undergoes endocytosis