Structure of the Cell Membrane

1.         All eukaryotic cells are enveloped by a semi-permeable plasma membrane which serves as a barrier, separating the contents of the protoplasm from the extracellular environment.

2.         As such, it

a.            maintains the integrity of the cell and keep constant the intracellular millieu by preventing mixing of its content with extracellular fluid.

b.            provides a suitable environment (pH, enzymes, etc) for the cell to carry out its specific functions.

c.            prevents the entry of toxic substances which are detrimental to the normal functioning of the cell.

d.            prevents the intermediate by-products and waste products of metabolic pathways from entering the extracellular fluid which may consequently find its way to the bloodstream.

e.         in short, it separates the variable and potentially hostile environment outside the cell from the relatively constant milieu within the cell and is the communication link between the cell and the surroundings.

f.            Structural support:

i.            intracellular proteins of the cytoskeleton are linked to cell membrane proteins to maintain cell shapes.

ii.            specialized connections between adjacent cells or between cells and the extracellular matrix stabilize the assembly of cells into tissue.

iii.         a few membrane lipids participate in communication between the extracellular environment and the cell.

3.         The cell membrane is about 7.5 to 10 nm thick.

4.         Fluid mosaic model of membrane structure:

a.         the membrane consists of a phospholipid bilayer which is a thin flim of lipids only two molecules thick that is continuous over the entire cell surface.

b.         with large globular protein molecules being interspersed among the phospholipid bilayer.

c.         the proteins are either inserted into the phospholipid bilayer or bound to the membrane surface.

d.         this model of the membrane structure is termed as the trilaminar structure, which is also called the unit membrane in which it is proposed that all cell membranes have a similar structure.

5.         The three major lipid components of eukaryotic cell membranes are:

a.            phosphoglycerides

b.            sphingolipids

c.            cholesterol

6.            Phospholipids:

a.         they are amphipathic, consisting of :

i.          a polar, hydrophilic head

ii.          a non-polar, hydrophobic tail.

b.         the polar heads are mainly derived from glycerol conjugated to a nitrogenous compound such as choline, ethanolamine or serine via a phosphate bridge.

c.         The phosphate group is negatively charged whereas the nitrogenous group is positively charged.

d.         The non-polar tail of the phospholipid molecule consists of two long-chain fatty acids each covalently linked to the glycerol component of the polar head.

e.         one of the fatty acids is a straight-chain saturated fatty acid while the other is an unsaturated fatty acid which is ‘kinked’ at the position of the unsaturated bond.

7.         Other arrangement of phospholipids:

a.            micelles:

i.          these are small droplets of phospholipid, arranged so that the interior is filled with hydrophobic fatty acid tails

ii.          they are important in the digestion and absorption of fats in the digestive tract.

b.            liposomes:

i.          they are larger spherical structures with an exterior composed of a phospholipid bilayer.

ii.          this arrangement leaves a hollow center with an aqueous core.

iii.         this core can be loaded with water-soluble molecules.

iv.            liposomes are being tested as a medium for the delivery of drugs through the skin.

8.            Because of their amphipathic nature, phospholipids in aqueous solution will spontaneously form a bilayer with the hydrophilic heads directed outwards in contact with the surrounding aqueous medium and the hydrophilic tails forced inward.

9.         Fluid nature of the Plasma Membrane:

a.         the weak intermolecular forces (hydrophobic interactions) which hold the bilayer together:

i.          allow individual phospholipid molecules to move relatively freely within each layer.

ii.          and sometimes to ‘filp’ between layers.

b.            dynamic structures as constituents are being changed constantly by the twin processes of exocytosis and endocytosis.

c.         the fluidility and flexibility of the membrane is increased by the presence of unsaturated fatty acids which prevent close packing of the hydrophobic tails.

d.         many proteins within the membrane are freely mobile within the plane of the phospholipid.                           

10.            Cholesterol:

a.         found in the central lipid portion of the lipid bilayer.

b.         make the membrane impermeable to small water-soluble molecules and keeps the membrane flexible over a wide range of temperatures.

c.         is amphipathic and have a kinked conformation.

d.            prevents too close packing of the phospholipid fatty acid tails while at the same time filling the gaps between the ‘kinks’ of the unsaturated fatty acid tails.

e.         they thus regulate the fluidity and stabilise the phospholipid bilayer.

11.            Membrane Proteins:

a.            constitute about 50 % of the plasma membrane:

b.         of two types, integral and peripheral proteins.

12.           Functions of Membrane Proteins:

a.            Structural proteins:

i.          they link the membrane to the cytoskeleton in order to maintain the shape of the cell, eg. the microvilli of transporting epithelia  whose shape and movement is maintained by the cytoskeleton.

ii.          form part of the cell-to-cell connections that hold tissues together.

iii.            membrane-spanning proteins link cytoskeleton fibers inside the cell to collagen and other fibers in the extracellular matrix.

b.            Enzymes:

i.            membrane-associated enzymes catalyze chemical reactions that take place on the cell’s external surface or just inside the cytoplasm.

ii.            enzymes on the luminal surface of cells in the small intestine are responsible for the digestion of peptides and carbohydrates.

iii.            enzymes attached to the intracellular surface of many cell membranes play an important role in the transfer of signals from the extracellular environment to the cytoplasm of the cell.

c.            Receptors:

i.            receptor proteins on the outer surface of the cell are part of the body’s chemical signaling system.

ii.          each receptor is specific for a certain molecule or family of related molecules.

iii.         the molecule that binds to a receptor is called its ligand whose binding triggers the activation of a membrane enzyme.

iv.         one example of a ligand is insulin, which combines with an insulin receptor on a cell membrane in order to exert its effects.

d.            Channel Proteins:

i.          these proteins are made of amino acid chains that zigzag back and forth across the membrane, creating a cluster of protein cylinders surrounding the water-filled channels.

ii.          the diameter of these channels is narrow enough that movement through them is restricted to water, ions, and small molecules like urea.

iii.         the selectivity of a channel may restrict molecules based on electrical charge: if a channel is lined with polar amino acids with a certain charge, ions with the same charge will be repelled while ions of opposite charge will be attracted.

iv.            membrane channels have regions that act like ‘gates’ that swing to open and close the channel.

v.         open channels, also known as leak channels, spend most of their time in an open state, allowing ions to move back and forth across the membrane without regulation.

vi.         gated channels most of their time in a closed state and their opening and closing is controlled by messenger ligands.

e.         Carrier Proteins:

i.          these membrane transporters bind with specific molecules and carry them across the membrane by changing conformation or shape.

ii.          the molecules being transported across the membrane are called substrates.

iii.         the substrate binds to the carrier on one side of the membrane which changes the conformation of the protein so that one gate closes and the other open.

iv.         as a result the channels opens to the opposite side of the membrane, releasing the substrate to the other side.

f.            Differences between carrier and channel proteins:

i.          carrier proteins does not create a continuous passage between the inside and outside of the cell, in contrast to channel proteins.

ii.          the molecule binds to a carrier protein first instead of traveling through it as in channel proteins.

iii.         channel proteins allow more rapid transport across membranes than carrier proteins.

iv.         carriers are more selective about what they transport – specific binding sites for substrate.

13.       Integral Proteins:

a.         some are partially embedded in the lipid layer, so that they may protrude from either the outer and inner surface.

b.            transmembrane proteins are large enough to extend across the two lipid bilayers and protrude from either the outer or inner surface.

c.            depending on the number of times they span the membrane, from one side to the other, they are termed one-pass or multipass transmembrane proteins.

d.         the uncharged, hydrophobic portions of proteins are usually located in the interior of the membrane, whereas the charged, hydrophilic portions are located on the surfaces.          

e.            functions as:

i.          pumps: actively transporting ions across the membrane.

ii.          carriers: transporting substances down electrochemical gradients by facilitated diffusion.

iii.         ion channels: which, when activated, permit the passage of ions into or out of the cell.

iv.            enzymes: integral proteins that are present on only one side of the membrane serve primarily as enzymes that activate or inactivate various metabolic processes.

14.            Peripheral Proteins:

a.            attached  only to the surface of the membrane, usually on the integral proteins.

b.         binding of  protein on membrane surface:

i.          bound to an integral protein.

ii.            electrostatic binding to the lipid bilayer.

iii.            attached by a short hydrophobic amino acid chain.

iv.            attached by covalently bound lipid.

c.         function as:

i.            receptors: that bind neurotransmitters and hormones, initiating physiologic changes inside the cell.

ii.            enzymes: catalyzing reactions at the surface of the membrane.

iii.            adsorption of molecules to the cell surface.

iv.            formation of  intercellular adhesions.

v,         cell to cell recognition: glycoproteins that function in antibody processing and distinguishing self from non-self.

v.            provides mechanical and chemical protection for the plasma membrane.

15.            Peripheral proteins that bind to the intracellular surface of the membrane contribute to the cytoskeleton.

16.            Peripheral proteins that bind to the extracellular surface of the membrane contributes to the glycocalyx.

17.            Glycocalyx:

a.         many of the membrane proteins and some of the membrane lipids are conjugated with short chains of polysaccharide.

b.         these glycoproteins and glycolipids respectively project from the surface of the bilayer forming a fuzzy outer coating representing the glycocalyx.

18.            Underlying most cells is a thin, fuzzy layer plus some fibrils that collectively make up the basement membrane or the basal lamina, which is made up of a collagen derivative plus glycoproteins.

19.       In epithelial cells, the enzymes in the cell membrane on the apical surface differ from those in the cell membrane on the basal surface; the cells are polarized.

20.            Capping:

a.         under certain circumstances, proteins can accumulate at one region of the plasma membrane, forming a localized aggregations of proteins:

b.         the aggregation of receptors at the site of endocytosis.

c.         this process is termed capping and is controlled by cytoskeletal microfilaments and other proteins.