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PLASMA MEMBRANE
STRUCTURE, FUNCTION AND TRANSPORT
1. S.N: structure of cell membrane- Feb 2008
2. Explain the fluid mosaic model of membranes. Pon Nov 2010
Structure:
1. The cell membrane (also called the plasma membrane, plasmalemma, or
phospholipid bilayer) is the interface between the cellular machinery inside
the cell and the fluid outside.
2. Plasma membranes form closed compartments around cellular protoplasm to
separate one cell from another and thus permit cellular individuality.
Models of membrane structure:
The lipid bilayer was originally proposed by Davson and Danielle in 1935. Later,
the structure of the biomembranes was described as a fluid mosaic model (Singer
and Nicolson, 1972).It is a more recent and acceptable model for membrane
structure.
Lipid bilayer model:
1. Membranes are complex structures composed of lipids, proteins, &
carbohydrate-containing molecules. The carbohydrates are present as
glycoproteins and glycolipids. The Major lipids in mammalian membranes are
phospholipids, glycosphingolipids & cholesterol.
2. Membranes are sheet like structures consisting of an asymmetric lipid bilayer
with distinct inner and outer surfaces. These sheet-like structures are
noncovalent assemblies that form spontaneously in water due to the
amphipathic nature of lipids. Many different proteins are located in
membranes, where they carry out specific functions.
3. All major lipids in membranes contain both hydrophobic and hydrophilic
regions and are therefore termed amphipathic. If the hydrophobic region were
separated from the rest of the molecule, it would be insoluble in water but
soluble in oil. Conversely, if the hydrophilic region were separated from the
rest of the molecule, it would be insoluble in oil but soluble in water.
4. Diagrammatic representation of a phospholipid:
1. Phospholipids that contain glycerol are called glycerophospholipids (or
phosphoglycerides).
2. Sphingophospholipids eg. sphingomyelin contains phospholipid and the
amino alcohol sphingosine, rather than glycerol.
3. Part of the molecule is hydrophobic, or water insoluble; and a part is
hydrophilic, or water soluble. Such molecules aredescribed as
amphipathic

4. The phospholipids are arranged in bilayers with the polar head groups
oriented towards the extracellular side and the cytoplasmic side. The
tail part forms the hydrophobic core. Lipid bilayers are formed by selfassembly, driven by the hydrophobic effect. The closed bilayer is
impermeable to watersoluble molecules.

5. Membranes contain proteins, which form channels for the movement of


ions and small molecules or serve as transporters formolecules that
otherwise could not pass the bilayer.
Fluid mosaic model:
1. The membrane is basically formed of lipid bilayer. The lipid bilayer shows free
lateral movement of its components, hence the membrane is said to be fluid in
nature. Fluidity enables the membrane to perform endocytosis and exocytosis.
2. The components do not freely move from inner to outer layer, or outer to inner
layer (flip-flop movement is restricted). During apoptosis (programmed cell
death), flip-flop movement occurs.

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3. The cholesterol and unsaturated cis fatty acids content of the membrane
alters the fluidity of the membrane. When cholesterol concentration increases,
the membrane becomes less fluid on the outer surface, but more fluid in the
hydrophobic core.

4. Membrane Proteins:
1. Membranes contain Integral & Peripheral Proteins
2. Integral membrane proteins: These proteins are deeply embedded in
the membrane. Thus portions of these proteins are in Van der Waals
contact with the hydrophobic region of the membrane.
3. Peripheral membrane proteins: These may be weakly bound to the
surface of the membrane by ionic interactions or by hydrogen bonds
that form between the proteins and the polar heads of the membrane
lipids. They may also interact with integral membrane proteins. They
can be removed without disrupting the membrane.
4. The special peripheral membrane proteins that participate in this stability of red cells
are:
1. Spectrin
2. Actin
5. Transmembrane proteins: Some of the integral proteins span the whole
breadth of the membrane and are called as transmembrane proteins.
The hydrophobic side chains of the amino acids are embedded in the
hydrophobic central core of the membrane. These proteins can serve as
receptors for hormones, neurotransmitters, tissue specific antigens,
growth factors, etc.
5. Carbohydrates in membrane:

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1. Approximately 5 per cent of the weight of cell membranes is
carbohydrate, in the form of glycoproteins and glycolipids.
2. Glycophorin is a major integral membrane glycoprotein of human
erythrocytes.
3. Manv animal cell membranes have thick coating of complex
polysaccharides referred to as glycocalyx.
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Types of Lipids Present in Biomembranes:


1. Fatty acids: They are major components of most membrane lipids. Oleic
acid is the most abundant unsaturated fatty acid in animal membrane
lipids; others are arachidonic acid, linoleic and linolenic acids. The
degree of unsaturation determines the fluidity of the membranes.
2. Glycerophospholipids: They are another group of major components of
biomembranes. Phosphatidylethanol amine (cephalin),
phosphatidylcholine (Lecithin) and phosphatidylserine are among the
most of common glycerophospholipids.
3. Sphingolipids: They comprise another group of lipids found in biological
membranes specially in the tissues of nervous system. There are three
types of sphingolipids sphingomyelin, cerebrosides and gangliosides.
4. Cholesterol: Cholesterol is another common component of the
biomembranes of animals but not of plants and prokaryotes. Cholesterol
helps to regulate fluidity of animal membranes.

Additional Special Features of Some Membranes:


1. Lipid rafts: They are dynamic areas of the lipid bilayers enriched in cholesterol
and sphingolipids. Function: They are involved in signal transduction and
possibly other processes like endocytosis and binding of viral pathogen.
2. Caveolae: They are probably derived from lipid rafts. Many of the caveolae
contain a special protein called caveolin-1, which may take part in signal
transduction and membrane transport.
Specialised membrane structures:
1. Tight Junction: When two cells are in close approximation, in certain areas,
instead of 4 layers, only 3 layers of plasma membranes are seen. This tight
junction permits calcium and other small molecules to pass through from one
cell to another through narrow hydrophilic pores. Some sort of communication

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between cells thus results. Absence of tight junction is implicated in loss of
contact inhibition in cancer cells.
2. Myelin Sheath: It is made up of the membrane of Schwann cells of the central
axon. Myelin is composed of sphingomyelin, cholesterol and cerebroside. In
multiple sclerosis, demyelination occurs at discrete areas, velocity of nerve
impulse is reduced, leading to motor and sensory deficits.
3. Microvilli of intestinal epithelial cells and pseudopodia of macrophages are
produced by membrane evagination. This is due to the fluid nature of
membranes.
4. Membranes of endoplasmic reticulum, nucleus, lysosomes and outer layer of
mitochondria may be considered as variants of plasma membrane.
5. Cytoskeleton: Human body is supported by the skeletal system; similarly the
structure of a cell is maintained by the cytoskeleton present underneath the
plasma membrane. The cytoskeleton is responsible for the shape of the cell,
its motility and chromosomal movements during cell division. The cytoskeleton
is made up of a network of microtubules and microfilaments, which contain the
proteins spectrin and ankyrin. Tubules consist of polymers of tubulin.
Functions of membrane:
1. The plasma membrane has selective permeability and acts as a barrier,
thereby maintaining differences in composition between the inside and outside
of the cell. The selective permeability is provided mainly by channels and
pumps for ions and substrates.
2. The plasma membrane also exchanges material with the extracellular
environment by exocytosis and endocytosis, and there are special areas of
membrane structurethe gap junctionsthrough which adjacent cells
exchange material.
3. In addition, the plasma membrane plays key roles in cell cell interactions and
in transmembrane signalling.
4. It is metabolically very active
5. The transmembrane proteins serve as receptor sites for hormones,
neurotransmitters.

Membrane Transport

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1. The permeability of substances across cell membrane is dependent on their
solubility in lipids and not on their molecular size. Water soluble compounds
are generally impermeable and require carrier mediated transport. An
important function of the membrane is to withhold unwanted molecules, while
permitting entry of molecules necessary for cellular metabolism.
2. Classification of Transport mechanisms:

a. Passive transport
i. Simple diffusion
ii. Facilitated diffusion.
1. Transporters
2. Ion channels
b. Active transport
i. Pumps
1. Simple Diffusion: Solutes and gases enter into the cells passively. They are
driven by the concentration gradient. This process does not require energy.
Eg. Diffusion of gas like CO2 & O2
2. Facilitated Diffusion:
a. Here also the solute moves along the concentration gradient but occurs
through the mediation of carrier or transport proteins.
b. Specific carrier proteins for the transport of glucose, galactose, leucine,
phenyl alanine etc. have been isolated and characterized.
c. They can operate bidirectionally and do not require energy.
d. Mechanism:
a. Ping and pong states:
i. The carrier molecules can exist in two conformations, Ping and
Pong states. In the pong state the active sites are exposed to
the exterior, when the solutes bind to the specific sites. Then
there is a conformational change. In the ping state, the active
sites are facing the interior of the cell, where the
concentration of the solute is minimal. This will cause the
release of the solute molecules and the protein molecule

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reverts to the pong state.
ii. Hormones regulate facilitated diffusion. For instance, insulin
increases glucose
transport in muscle and adipose tissue;
amino acid transport in liver and other tissues

iii. Aquaporins:
1. Water crosses the membrane through pores called
aquaporins; They are a family of membrane channel
proteins that serve as selective pores through which
water crosses the plasma membranes of cells. impaired
function of these channel is the basis for diabetes
insipitus.

2. Ion Channels
a. Membranes have special devices called ion channels. They are
specialized protein molecules and work like a gate. They are

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important for nerve conduction, synaptic transmission and secretion
of some substances. The channels generally remain closed, but in
response to stimulus, they open allowing rapid flux of ions down the
gradient. Hence this regulation is named as "gated".
b. Salient features of ion channel are:
i. They are transmembrane proteins
ii. Selective for one particular ion
iii. Regulation of activity is done by voltage-gated, ligand-gated
or mechanically gated mechanisms
iv. Different channels are available for Na+, K+,Ca++ and Cl-v. Transport through the channel is very quick
c. Channelopathies are a group of disorders that result from
abnormalities in the proteins forming the ion pores or channels. A
few examples are cystic fibrosis (chloride channel), Liddle's
syndrome (sodium channel) and periodic paralysis (potassium
channel).
d. Examples of ion channels:
i. Ligand gated channels: Binding of a ligand to a receptor site
on the ion channels is called ligand gated channels. Examples:
1. Acetyl choline receptor is the best example for ligand
gated ion channel. Ach receptors present in post
synaptic membrane helps in the generation of action
potential.
2. Calcium channels: are in the membrane of sarcoplasmic
reticulum and this allows ca to enter into muscle cells.
Ca channel blockers are used in treating hypertension.
Amelogenin: this is a protein present in teeth and
functions as calcium channel to regulate calcium
mineralization.
ii. Voltage gated channel:
1. These channels are opened by membrane
depolarization. Voltage gated sodium channels and
voltage gated potassium channels are the common
examples. These are seen in nerve cells and are
involved in the conduction of nerve impulses.

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iii. Ionophores: They transport antibiotics that increase the
permeability of membrane to ions by acting as channel
formers. They are produced by micro organisms and used as
antibiotics e.g. Valinomycin, Gramicidin.
iv. Valinomycin allows potassium to permeate mitochondria and
so it dissipates the proton gradient; hence it acts as an
uncoupler of electron transport chain
Ionophores

7. Active Transport:
1. Active transport occurs against a concentration gradient and this is
dependent on the supply of metabolic energy (ATP).
2. If the process uses chemical energy, such as from adenosine triphosphate
(ATP), it is termed primary active transport. Secondary active transport
involves the use of an electrochemical gradient.
3. It is unidirectional. Specialised integral proteins called transporters are
involved
Examples of Primary active transport:
a. sodium potassium pumps:
a. It is the best example of active transport. The Na+-K+ pump is
responsible for the maintenance of high K+ and low Na+
concentrations in the cells. This is brought about by an integral
plasma membrane protein called Na+-K+ ATPase. It consists of two
, and two subunits.
b. This pump moves three Na+ ions from inside the cell to the outside
and brings two K+ ions from the outside to the inside for every

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molecule of ATP hydrolysed to ADP by the membrane-associated
ATPase. Ouabain and other cardiac glycosides inhibit this pump by
acting on the extracellular surface of the membrane.

b. Calcium Pump
a. An ATP dependent calcium pump functions to regulate muscle
contraction. A specialized membrane system called sarcoplasmic
reticulum is found in skeletal muscles which regulates the Ca++
concentration around muscle fibers.
b. In resting muscle the concentration of Ca++ around muscle fibers is
low. But stimulation by a nerve impulse results in a sudden release of
large amounts of Ca++. This would trigger muscle contraction.
Secondary active transport:
It is also known as coupled transport or co-transport: The transport systems
may be divided into 2 categories.
a. Uniport system: This involves the movement of a single molecule through
the membrane e.g. transport of glucose to the erythrocytes.
b. Cotransport system : In cotransport, the transport of a substance through
the membrane is coupled to the spontaneous movement of another
substance. The symport and antiport systems are good examples of
cotransport system.

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a. Symport system: The simultaneous transport of two different
molecules in the same direction e.g. transport of Na+ and glucose to
the intestinal mucosal cells from the gut.
b. Antiport system: The simultaneous transport of two different
molecules in the opposite direction e.g exchange of Cl- and HCO3 in
the erythrocytes.
c. Uniport, symport and antiport systems are considered as secondary active
transport systems.

d. Proton pump in the stomach : This is an antiport transport system of gastric


parietal cells. lt is brought out by the enzyme H+-K+ ATPase to maintain
highly acidic (pH=l) conditions in the lumen of the stomach. Proton pump
antiports two cytoplasmic protons (2H+) and two extracellular potassium
(2K+) ions for a molecule of ATP hydrolysed. The chloride ions secreted by
Clchannels combine with protons to form gastric HCI.Clinical Applications
a. In Hartnup's disease, transport mechanisms for amino acids are
defective in intestine and renal tubules.
b. In cystinuria, renal reabsorption of cysteine is abnormal
c. Renal reabsorption of phosphate is decreased in vitamin D resistant
rickets.
d. Diseases due to abnormalities of transport systems include familial
hypercholesterolemia, cystic fibrosis, congenital long QT syndrome,
Wilson disease, I-cell disease, hereditary spherocytosis and
paroxysmal nocturnal hemoglobinuria, etc
Transport of Macromolecules:

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The mechanism of transport of macromolecules such as proteins, hormones,
immunoglobulins, low density lipoproteins (LDL) and even viruses takes place
across the membrane by two independant mechanisms.
Exocytosis:
a. Most cells release macromolecules to the exterior by the process called
exocytosis. This process is involved in membrane remodelling when the
components synthesised in the Golgi apparatus are carried in vesicles to
the plasma membrane.
b. The movement of the vesicle is carried out by cytoplasmic contractile
elements in the microtubular system. Release of insulin by beta cells of
Langerhans and release of acetyl choline by presynaptic cholinergic nerves
are examples of exocytosis
Endocytosis:
a. It is the mechanism by which cells internalize extracellular
macromolecules, to form an endocytic vesicle. This requires energy in the
form of ATP as well as calcium ions in the extracellular fluid. Cytoplasmic
contractile elements take part in this movement. In general, plasma
membrane is invaginated, enclosing the matter. This forms the endocytic
vesicle.
b. The endocytosis may be pinocytosis or phagocytosis or receptor mediated
endocytosis. Pinocytosis literally means drinking by the cell'. Cells take up
fluid by this method.
c. Phagocytosis: The term is derived from the Greek word "phagein" which
means to eat. It is the engulfment of large particles such as bacteria by
macrophages and granulocytes.
d. The selective or adsorptive pinocytosis is receptor mediated; also called as
absorptive pinocytosis. Low Density Lipoprotein (LDL) is an example. LDL
binds to the LDL receptor and the complex is later internalized.

Endocytosis
Exocyosis
a. Clinical aspect:

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a. Chronic granulomatous disease has been recently implicated due to
defective phagocytosis and respiratory burst.
b. Receptor mediated endocytosis with viruses are responsible for many
diseases, viz.
i. Hepatitis virus affecting liver cells
ii. Poliovirus affecting motor neurons
iii. AIDS affecting T cells.
iv. Iron toxicity also occurs with excessive uptake due to endocytosis.
c. Lebers Hereditary Optic Neuropathy (LHON): In this disease mutations in
genes encoding mitochondrial membrane proteins involved in oxidative
phosphorylation can produce neurologic and vision problems.
d. Cystic fibrosis transmembrane protein (CFTR) is a cyclic AMP dependant
regulatory protein for chloride channel. Genetic mutation produces an
abnormal CFTR, which produces an abnormality of membrane Cl
permeability resulting to increased viscosity of many bodily secretions.