Living cells have a cell membrane. Also termed as plasma or biological membranes. Cell membranes are double lipid layers that also include membrane proteins. Cell membranes helps to protect the cellular components from the environment. Membrane also regulate the transport of the material into the cell and to outside from the cell. In plants and prokaryotes, the plasma membrane is an internal protective layer to the inner side of a cell wall. Eukaryotes do not have this cell wall. In eukaryotes, the membrane also forms the boundary of cellular organelles,

The cell membrane has several other specific names based on its composition of lipids and proteins, such as “sarcolemma” in the myocytes and “oolemma” in the oocytes. The plasma membrane is only 5-10 nm wide, so it can not be detected with an optical microscope. It can be observed only under the transmission electron microscope as a trilaminar structure which is a layer of hydrophobic phospholipid tails interspersed with two layers of hydrophilic heads.

Table of Contents

• Functions of Cell Membrane
  • Diffusion
  • Osmosis
  • Mediated Transport
  • Bulk Transport
    • Transport by endocytosis
    • Transport by exocytosis
  • Intercellular interaction
  • Cell signalling
• Theories
  • Quincke
  • Danielli and Davson Sandwich Model (1935)
  • Robertson’s unit membrane model (1959)
  • S.J.Singer and G.L.Nicolson’s fluid mosaic model (1972)
• Composition of Cell membrane
  • Membrane-Lipids
    • Fatty Acids
    • Phosphoglycerides (Glycerophospholipids)
    • Sphingolipids
      • ceramide
      • sphingomyelin
      • Glycolipid
    • Cholesterol
  • Membrane-Protein
    • Integral membrane proteins
      • Glycophorin
      • Bacteriorhodopsin
    • Peripheral membrane proteins
    • Lipid-anchored membrane proteins
  • Membrane carbohydrates
    • • Glycolipids
      • Glycoproteins

Functions of Cell Membrane

Membranes are not just inert barriers but are dynamic, semi permeable and have a number of biochemical and physiological functions. This diversity in function is due to the variability in composition of lipid and protein in the membranes. Different biological membranes are associated with various functions that can be summarized as given below.

Diffusion

Small molecules such as carbon dioxide, oxygen (O₂), and water can diffuse by passive transport, while membrane transport proteins allow only certain molecules and ions to diffuse through the plasma membrane.

Osmosis

The cytoplasm of a cell contains ions and molecules, such as sugars and amino acids, dissolved in water. The mixture of these substances and water is called an aqueous solution. Water, the most common of the molecules in the mixture, is the solvent, and the substances dissolved in the water are solutes. The ability of water and solutes to diffuse across membranes has important consequences.

Mediated Transport

Nutrients or some molecules are moved across the membrane by special proteins called transport proteins or permeases which specifically recognize and transport only a limited group of chemical molecules, often even only a single type of molecules.

Bulk Transport

The large molecules that cannot cross the hydrophobic barrier of lipid bilayer. In this case, the plasma membrane extends outward and envelops food particles.

Transport by endocytosis

Endocytosis is the process where cells absorb molecules by engulfing them. Cells use three major types of endocytosis: phagocytosis, pinocytosis, and receptor-mediated endocytosis.

Transport by exocytosis

The reverse of endocytosis is exocytosis, the discharge of material from vesicles at the cell surface. In animal cells, exocytosis provides a mechanism for secreting many hormones, neurotransmitters, digestive enzymes, and other substances.

Intercellular interaction

The plasma membrane of multicellular organisms mediates the interactions between a cell and its neighbours at its outer edge. The plasma membrane allows cells to recognize and signal one another, to adhere, and to exchange materials and information.

Cell signalling

The plasma membrane plays important role in the response of a cell to external stimuli, a process known as signal transduction. Membranes possess receptors that combine with specific molecules (or ligands) having a complementary structure.

Theories

Quincke

• Quincke was the first to perceive the lipid nature of cell membranes. With time many researchers have proposed models for the cell membrane.

Danielli and Davson Sandwich Model (1935)

• The membrane structure in which a lipid bilayer was coated with hydrated proteins on its either side.
• The mutual attraction between the hydrocarbon chains of the lipids and electrostatic forces between the protein and the “head” of the lipid molecules helps to maintain the stability of the membrane.
• They also predicted that the lipid bilayer to be about 6.0 nm in thickness, and each of the protein layer of about 1.0 nm in thickness, giving a total thickness of about 8.0 nm.
• The Danielli-Davson model got support from electron microscopy.
  • membrane consists of two dark layers (electron dense granular protein layers), both separated by a lighter area in between (the central clear area of lipid bilayer).
  • The total thickness of the membranes then turned out to be about 7.5 nm.

Robertson’s unit membrane model (1959)

This model stated that the central layer of plasma membranes is made up of the hydrocarbon chains of lipids and the proteins constitute the dense surrounding layers on both sides when viewed through an electron microscope.  

S.J.Singer and G.L.Nicolson’s fluid mosaic model (1972)

• The plasma membrane contains a bimolecular lipid layer, both surfaces of which are interrupted by protein molecules.
• Proteins are spread there in a mosaic pattern. They can be of different types depending on their location and role.
  • 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 and they are termed as glycoproteins.
• Some lipids of outer surface contain oligosaccharide chains are glycolipids.

• 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.

Composition of Cell membrane

The major components of biological membranes are lipids and proteins and to some extent carbohydrates and networking fibers.

Membrane Lipids establish the physical integrity of the membrane and create an effective barrier to the rapid passage of hydrophilic materials such as water and ions.

Membrane Proteins embedded in the phospholipid bilayer have a number of functions, including moving materials through the membrane and receiving chemical signals from the cell’s external environment.

Membrane Carbohydrates associated with membranes are attached either to the lipids or to protein molecules. They are located on the outside of the plasma membrane, where they protrude into the environment, away from the cell. Different cell types exhibit different varieties of these glycoproteins and glycolipids on their surfaces, which act as cell identity markers.

Membrane-Lipids

• Lipids are insoluble in water and soluble in organic solvents.
• They are amphipathic molecules with a hydrophobic and a hydrophilic region.
• Establish the physical integrity of the membrane
• Create an effective barrier for hydrophilic materials such as water and ions.
• The main classes of lipids present in cell membrane that generally constitute the major lipid portion of membranes but their composition varies among different membranes are as follows :-
  • Fatty Acids
  • Glycerophospholipids
  • Sphingolipids
  • Sterols
  • Galactolipids and Sulpholipids present specifically in thylakoid membranes in chloroplasts
  • Glycerol Di Alkyl Tetraether Lipids present only in Archaebacteria.
• Eukaryotic membrane lipids are glycerophospholipids, sphingolipids, and sterols.

Fatty Acids

• Fatty acids do not exist free in biological membranes but only as components of phospholipids, glycolipids, etc.
• The fatty acids present in most membranes are CH₃–(CH₂)_n– COOH, (Where n= 12 to 22), 16- and 18-carbon fatty acids are the most common.
• Fatty acids can be saturated or unsaturated.
• If the fatty acids are unsaturated, the configuration around the double bond is cis in most cases and the number of double bonds in a fatty acid molecule can be 1 to 6.
• The unsaturated fatty acids prevent tight packing of the fatty acid chains leading to lowering of melting temperature and increase in membrane fluidity.

The common fatty acids found in membranes are:-

• Myristic acid (C14:0)
• Palmitic acid (C 16:0)
• Stearic acid (C18:0)
• Oleic acid (C18:1)
• Linoleic acid (C18:2)
• Arachidonic acid (C20:4)

Phosphoglycerides (Glycerophospholipids)

• Glycerol phospholipids are the major constituents of biological membranes in animal, plant and bacteria.
• Phosphoglycerides often contain one unsaturated, one saturated fatty acyl chain and phosphate Because all these are attached on a glycerol backbone, they are called phosphoglycerides.
• The third carbon on the glycerol backbone is attached to a highly polar organic alcohol (‘X’). Because this alcohol is attached by a phosphate group, the molecule is called a phospholipid.
• The two fatty acid chains at C-1and C-2 of glycerol can be the same or different .One of them, usually at C-1 is saturated while the other at C-2 is unsaturated or cyclic fatty acid.
• The chain length and the number of double bonds in the two fatty acyl chains can vary as also the nature of the ‘X’ group.
• Thus, different combinations of phospholipids molecules can exist in a membrane and their number is very large.

Major phospholipids include the neutral phospholipids (no net charge at neutral pH) such as

• Phosphatidyl choline (PC)
• Phophatidyl ethanolamine (PE)
• Sphingomyelin

Acidic phospholipids (5-20%) are negatively charged that include

• Phosphatidyl inositol (PI)
• Phosphatidyl serine (PS)
• Phosphatidyl glycerol
• Cardiolipin and Sulfolipids

• The plasmalogens are a group of phosphoglycerides that contain one fatty acyl chain, attached to glycerol by an ester linkage, and one long hydrocarbon chain, attached to glycerol by an ether linkage (COOC).
• These molecules constitute about 20 percent of the total phosphoglyceride content in humans. Their abundance varies among tissues and species but is especially high in human brain and heart tissue.

Sphingolipids

• Sphingolipids are the second major constituents of the membranes.
• These are derivatives of sphingosine (an amino alcohol that contains a long hydrocarbon chain).
• The sphingosine-based lipids have additional groups esterified to the terminal alcohol of the sphingosine moiety.

Types of sphingolipids are

ceramide

consist of sphingosine linked to a fatty acid by its amino group.

sphingomyelin

consists of a phosphocholine head group, a sphingosine, and a fatty acid  and is the only phospholipid of the membrane that is not built with a glycerol backbone.

Glycolipid

can contain either glycerol or sphingosine backbone, and always have a sugar such as glucose in place of the phosphate head found in phospholipids.

Types of glycolipids are

•  Cerebroside: If the carbohydrate is a simple sugar, the glycolipid is called a cerebroside;
•  Ganglioside: if it is a small cluster of sugars, the glycolipid is called a ganglioside.
•  Galactocerebroside: The nervous system is particularly rich in glycolipids. The myelin sheath contains a high content of a particular glycolipid, called galactocerebroside, which is formed when a galactose is added to ceramide.

Cholesterol

• Cholesterol is a component of the animal cell membrane. It is a type of lipid, and is called steroids.
• In many membranes, the cholesterol is oriented parallel to the fatty acyl chains of the phospholipids and the OH-group interacts with the hydrophilic groups of the adjacent lipids.
• These cholesterol molecules are positioned between the phospholipids in the membrane.
• The hydrophobic rings of a cholesterol molecule are flat and rigid, and they interfere with the movements of the fatty acid tails of the phospholipids.

Cholesterol is found in varying degrees in all animal cell membranes but is essentially absent from intracellular membranes. It is also absent in prokaryotes. The plant membranes contain Stigmasterol and the fungi Ergosterol.

Membrane-Protein

• In addition to the lipid bilayer, the plasma membrane also contains a number of proteins. The amount of protein differs between species and according to function, however the typical amount in a cell membrane is 50%.
• Membrane proteins are free to move within the lipid bilayer because of fluidity of the membrane.
• But, some of the proteins can also be confined to certain areas of the bilayer with enzymes.

Membrane proteins can be classified into three categories which is based on the nature of the membrane-protein interactions.

• Integral proteins
• Peripheral proteins
• Lipid-anchored

Integral membrane proteins

• These are also called as transmembrane proteins.
• Difficult to isolate in soluble form, require  detergent (ionic & nonionic).
• Integral proteinsspan a phospholipid bilayer and contain of three domains-cytosolic, exoplasmic and membrane-spanning domains.
• The cytosolic and exoplasmic domains have hydrophilic exterior surfaces that interact with the aqueous solutions on the cytosolic and exoplasmic faces of the membrane.
• The membrane-spanning domains contains many hydrophobic amino acids whose side chains protrude outward and interact with the hydrocarbon core of the phospholipid bilayer.
• The membrane-spanning domains consist of one or more α helices or of multiple β strands.

An example of integral proteins

Glycophorin

• It is a major erythrocyte membrane protein.
• It is a homodimer containing α helix in coiled-coiled conformation and is composed of uncharged amino acids.

Bacteriorhodopsin

• A protein found in a photosynthetic bacterium.
• Bacteriorhodopsins have serpentine membrane spanning domain.

Integral Proteins, on the other hand, require treatment with reagents such as detergents or organic solvents which disrupt hydrophobic interactions.

Peripheral membrane proteins

• Entirely outside either EC or IC face attached by non-covalent bond.
• Bound with electrostatic and H bond, not interact with hydrophobic interior of LB.
• Isolate by gentle extraction like high/low ionic strength solution or extreme pH, obstruct with weak non covalent interaction between protein- protein or protein- LB, remain LB intact.
• Weak electrostatic bond fibrillar network skeleton, Mechanical support.
• Peripheral proteins can be dissociated from isolated membranes by change in pH, ionic concentrations or treatment with EDTA or high salt concentrations under conditions which disrupt ionic (electrostatic bonds) or hydrogen bonds.

Lipid-anchored membrane proteins

• Protein covalently boud to lipid molecule called lipid anchored protein.
• FA linked protein (amide or thioester linkage)-Myristoyl (amide link of N terminal Gly)and Palmitoyl (thioester link of C or N terminus Cys). eg. Src-family kinases.
• Isoprenoid/Prenylgp(Cys at C terminus through Thioester linkage)- Farnesyl or Grenyl Geranyl gp linked protein.
• Gycosylated Phspholipid(amino acid at C terminus through amide link)- Glycosyl phosphotidyl inositol linkage are called GPI (Found outer leaflet or Exoplasmic)anchored protein.
• Outside lipid layer on either EC and IC surface but are covalently linked to lipid molecule called lipid anchored membrane protein.

Membrane carbohydrates

• Plasma Membrane carbohydrate content 2 to 10 %.
• Carbohydrates are located on the outer surface of the membrane and serve as recognition sites for other cells and molecules.
• Membrane-associated carbohydrates may be covalently bound to lipids or to proteins.

Glycolipids

• Consist of a carbohydrate covalently bound to a lipid.
• The carbohydrate units often extend to the outside of the membrane, where they serve as recognition signals for interactions between cells.
• For example, the carbohydrate of some glycolipids changes when a cell becomes cancerous. This change may allow white blood cells to target cancer cells for destruction.

Glycoproteins

• Consist of a carbohydrate covalently bound to a protein.
• The bound carbohydrates are oligosaccharide chains, usually not exceeding 15 monosaccharide units in length.
• Glycoproteins enable a cell to be recognized by other cells and proteins.