Describes the plasma membrane in detail, explains the each major component with its functions.
Transport mechanism across the cell is covered with detailed explanation with examples.
by Dr. N.Sivaranjani, MD

Biological membrane / Plasma membrane
Chemical composition of membranes:
Membranes are composed of
Lipids
Proteins
Carbohydrates -do not exist free form in membrane
Dr.N.Sivaranjani

Fluid mosaic model of plasma membrane
A lipid bilayer model – originally proposed
Davson and Danielle
Modified by Singer and Nicholson – is a more
recent and acceptable model for membrane structure.
Membrane essentially composed of a lipid bilayer.
Globular proteins are irregularly embedded in the lipid
bilayer
Carbohydrates
Lipid bilayer
Proteins
50 -80 Å
25 Å
Dr.N.Sivaranjani

Membrane Lipids
They are the basic structural components of cell
membranes.
Amphipathic lipids (containing hydrophobic &
hydrophilic groups) namely Phospholipids,
Cholesterol and
Glycolipids
Dr.N.Sivaranjani

Phospholipids
“Head” – Polar part (Hydrophilic) – phosphate
group
“Tail” – Non polar part
(Hydrophobic) –
long chain fatty acids
Even-numbered carbon
Head
16 or 18 carbons
Unbranched
Tail
can be saturated or
unsaturated
Phosphate gr
fatty acid
Dr.N.Sivaranjani

Saturated fatty acids — straight tails
unsaturated fatty acids – exist in the cis form in
membranes, make kinked tails.
Kink – Membrane becomes less tightly packed and
therefore more fluid.
Saturated FA
Unsaturated FA
Dr.N.Sivaranjani

Phospholipid
Most predominant molecular component of all membrane
Principal Phospholipid – phosphatidylcholine ( Lecithin) –50%
phosphatidylethanolamine (Cephaline)
phosphatidylserine
diphospatidyl glycerol (cardiolipin)
phosphatidylinositol
Sphingomyelin – prominent in myelin sheaths
Composition of lipids in membrane depends on the
physiological role played by the cell or organelle.
IMM – rich in cardiolipin and phosphatidyl ethanolamine.
Dr.N.Sivaranjani

Phosphatidylcholine and Sphingomyelin – outer leaflet of
the bilayer
Phosphatidylserine and Phosphatidylethanolamine – inner
leaflet.
Function of membrane lipids :
Acts as Permeability barriers.
Essential for the maintenance of fluidity of
membranes.
Dr.N.Sivaranjani

Cholesterol –
weakly amphipathic
abundant in mammalian cells, absent in prokaryotic cell
OH gr – faces exterior
cyclopentanophenanthrene ring – hydrophobic lipid phase.
Stability to membrane
Alters Fluidity of membrane
Dr.N.Sivaranjani

Glycolipids – 2-10%
present only on the
outer surface of membrane.
Single sugar or
branched oligosaccharide
attached to
sphingosine backbone of lipids.
Dr.N.Sivaranjani

Membrane Proteins
The main types of membrane proteins are
1. Integral membrane protein (intrinsic)
2. Peripheral membrane protein (extrinsic)
3. Trans membrane protein
Oligosaccharide chains
Integral protein
Peripheral
proteins
Trans
membrane
proteins
Dr.N.Sivaranjani

Integral proteins / intrinsic
proteins
Peripheral proteins / extrinsic
proteins
Embedded deeply in the bilayer Bound to external face of
membrane
Amphipathic -two hydrophilic ends
separated by an intervening
hydrophobic region that traverses
the hydrophobic core of the
bilayer
Bound to the hydrophilic regions of
specific integral proteins and head
groups of phospholipids
Hydrophobic /van der waals force Electrostatic & H bonds
Removed by detergents /organic
solvents.
No detergents
Salt solutions of different ionic
strength /pH is enough to remove
Spans the whole layer –
Transmembrane protein
Usually poses enzymatic activity
Ion channels
Carriers (transporters)
Receptors
Enzymes
Dr.N.Sivaranjani

Functions of membrane proteins
Ion channels Carriers (transporters) ,pumps
Structural component
Receptors -These proteins can serve as receptors for
hormones, neuro transmitters, growth factors etc.
Membrane based Enzyme
Tissue specific antigen
Dr.N.Sivaranjani

Membrane Carbohydrates
Minor component 5-8%
Occur as oligosaccharide that is Covalently bound to lipids
and proteins to form glycolipids and glycoproteins.
Never as free form
These are mostly – Glucose , Galactose , Mannose
N-acetyl glucosamine , fucose, sialic acid.
Glycocalyx – loose Carbohydrate layer on outer surface of
cell Dr.N.Sivaranjani

Functions –
Cell recognition and communication
Impart –ve charge to cell- repels other
particles.
helps in inter-cellular attachment / adhesion.
act as receptors
Cell identity markers (glycoproteins &
glycolipids) , antibody processing.
Dr.N.Sivaranjani

Membrane asymmetry
Mainly by protein – inserted in asymmetric fashion
Different Lipids composition in two leaflets
Oligosaccharide always project towards the
exterior
Dr.N.Sivaranjani

Polar head – external surface of the membrane
Non polar tail – inside the membrane
Lateral movement – Interior of membrane is fluid in
nature
Flip flop movement – restricted
Polar heads
Outer leaflet
Inner leaflet
Non polar
tails
Dr.N.Sivaranjani Aqueous phase

Membrane Fluidity
Influences its physiological function
Influenced by two major factors : Temperature and lipid
composition of the membrane
At Low temperature – fluidity is less
As the temperature increases – the hydrophobic side chains
undergo a transition from the ordered state to a
disordered one – increase in fluidity
The temperature at which the structure undergoes the
transition from ordered to disordered state is called the
“transition temperature” (Tm). Dr.N.Sivaranjani

Fluidity of membrane maintained by :
length of hydrocarbon chain
degree of unsaturation
Short chain FA – increase the fluidity
Long chain FA– decrease the fluidity
Unsaturated FA that exist in the cis configuration –
increase the fluidity
More the number of double bonds – greater is the fluidity.
Trans FA- decrease the fluidity of membrane
Dr.N.Sivaranjani

Cholesterol
Increase in cholesterol conc. – less fluid on outer surface,
more fluid on inner surface
Effect of cholesterol on fluidity is different with
different temperature.
At temperature below Tm – cholesterol increases fluidity
At temperature above Tm – cholesterol decreases fluidity
Dr.N.Sivaranjani

Functions of plasma membrane :
Transport of molecules – channels, pumps
Phagocytosis , pinocytosis – engulfing particles
Cell –cell communication – due to presence of carbohydrates
Cell signaling – cell membrane bound receptors, enzymes and
proteins
Protects the cellular organelles
Compartmentalization – segregates one part of the cell from
other
Membrane modifications for specialized functions – myelin
sheath of neurons, microvilli in intestine.
Dr.N.Sivaranjani

Artificial Membranes Model
Phospholipids of natural or synthetic origin that can be
treated (eg, by using mild sonication) to form spherical
vesicles in which the lipids form a bilayer.
Liposomes
Artificial membrane systems is used to study membrane
function
Liposomes can be made to entrap certain compounds inside
them
eg, drugs and isolated genes.
liposomes can be targeted to specific tissues or tumors
DNA entrapped inside liposomes appears to be less sensitive
to attack by nucleases – useful in gene therapy.
Dr.N.Sivaranjani

Transport across Cell membrane
Essential to maintain equilibrium of cell
Certain substances must move into the cell to support
metabolic reactions.
Other substances produced by the cell for export
or as cellular waste products must move out of the cell.
Dr.N.Sivaranjani

Types of Transport Mechanisms
Transport of Small molecules
Passive transport
Simple diffusion
Facilitated diffusion – Cotransport, Uniport
Active transport
Primary Active Transport
Secondary Active Transport
Transport of Large molecules
Exocytosis
Endocytosis
Dr.N.Sivaranjani

Types of transport mechanisms
1. Passive or simple diffusion
2. Carrier mediated :
2a. Facilitated diffusion
2b. Active transport
Dr.N.Sivaranjani

1. Passive or simple diffusion :
Very slow process
The solute passes from higher concentration to lower
concentration till equilibrium is reached.
does not require energy.
does not require the assistance of any carrier protein.
unidirectional.
Dr.N.Sivaranjani

Highly permeable to gases – CO2,NO,O2 (small ,
nonpolar)
Small uncharged molecule – ethanol , urea.
Moderately permeable to water
Dr.N.Sivaranjani

2. Carrier mediated system
Mediated by integral protein / Permeases/
porters/translocases.
Proteins are highly specific
Eg: in RBC – GLUT has high affinity for D-glucose but low
affinity for related sugars.
Specific for solute transport
Inhibited by structural analogues
Dr.N.Sivaranjani

2b. Facilitated diffusion.
resembles simple diffusion –
down the conc. Gradient,
does not require energy
requires a carrier transport protein.
operates bidirectional.
More rapid than simple diffusion
works as ping-pong mechanism.
Ex- Transport of Glucose by GLUT (GLUcose Transporters),
Transport of Amino acids
Dr.N.Sivaranjani

Ping-Pong” mechanism of facilitated diffusion
active sites are
exposed to exterior
active site
facing interior
of the cell
Dr.N.Sivaranjani

Uniport
Transport of single type of molecule in one direction.
Ex – transport of glucose in RBC by GLUT
Calcium pump.
Uniport
Dr.N.Sivaranjani

Co- transport system:
Symport
Transport of molecules in same direction.
Ex- Na- glucose transporter.
symport
Dr.N.Sivaranjani

Antiport
Two solutes are transported simultaneously in the opposite
directions
Eg. Chloride and bicarbonate ion exchange in the lungs.
Na+ pump.
Antiport
Dr.N.Sivaranjani

Active transport
Primary Secondary
Primary Active transport – Requires energy directly
eg: Na+K+pump,Ca pump
Secondary active transport – Requires energy indirectly
eg: Glucose transport into intestinal mucosal cell
Dr.N.Sivaranjani

Primary Active transport
occurs against concentration gradient
requires specific carrier protein or transport protein
Energy used directly from hydrolysis of ATP .
Saturated at higher conc. of solutes
Susceptible to inhibition by specific organic and inorganic
compounds.
Eg : – Na-K ATPase / Na Pump
– Ca-ATPase / Ca Pump
Dr.N.Sivaranjani

Sodium pump :
Low intracellular conc. of Na and high intracellular
conc. of K is maintained by Na-K ATPase / Na Pump
Made of 2 pairs of unequal subunit α2β2
ATPase – Integral protein
binding sites for ATP and Na – located inner side
K binding site – located outside.
Dr.N.Sivaranjani

Functions of Sodium Potassium Pump
Control cell volume
Renders nerve and muscle cells electrically excitable.
Active transport of amino acids and sugar.
Clinical aspects :
Sodium potassium ATPase is inhibited by digitalis (digoxin)
which increases force of contraction of heart muscle by
altering the excitability.
Ouabain is another inhibitor
Dr.N.Sivaranjani

Secondary active transport
Movement of a substance down its conc. gradient is
coupled to a second substrate against its conc.
gradient.
Eg: Glucose -Na+ symport – movement of Na+ down
its conc. gradient drags glucose against its conc.
gradient.
Energy for the transport comes from a secondary
source – stored in electrochemical gradient of Na+
Dr.N.Sivaranjani

Absorption of glucose, amino acids in intestinal mucosa
and also in proximal renal tubule.
Clinical aspects :
In cholera – severe dehydration occurs.
Oral rehydration therapy – contains NaCl & glucose.
The transport of glucose and Na+ across the intestinal
epithelium forces (via osmosis) movement of water
from the lumen of the gut into intestinal cells,
resulting in rehydration.
Glucose alone or NaCl alone would not be effective.
Dr.N.Sivaranjani

Transport of macromolecule
o Transport of macromolecule like proteins, hormones,
immunoglobulin, LDL and viruses
o Transport by formation of membrane bound vesicles
o Requires energy -ATP , Ca2+ ions.
1. Exocytosis
2. Endocytosis Phagocytosis
Pinocytosis
Receptor mediated endocytosis
Dr.N.Sivaranjani

Exocytosis
The cells release macromolecules to the exterior by
exocytosis.
The components are carried in the vesicles.
The inner membrane of the vesicle fuses with the outer
plasma membrane.
Outside
Inside the cell
Dr.N.Sivaranjani

Molecules released by exocytosis have at least three fates:
(1) They can attach to the cell surface and become
peripheral proteins, eg, antigens.
(2) They can become part of the extracellular matrix
eg, collagen and glycosaminoglycans.
(3) They can enter extracellular fluid and signal other cells.
Insulin, parathyroid hormone, and the catecholamines
are all packaged in granules and processed within cells, to be
released upon appropriate stimulation
Dr.N.Sivaranjani

Release of Trypsinogen by pancreatic acinar cell
Release of Insulin by beta cells of langerhans
Release of Acetyl choline by presynaptic cholinergic
nerves
Dr.N.Sivaranjani

Endocytosis
Endocytosis vesicles are formed when a segment of plasma
membrane invaginates enclosing a minute volume of ECF and its
contents.
Then fusion of the plasma membrane and neck sealing of the
vesicle occur.
Outside
Inside the cell
Dr.N.Sivaranjani

Endocytosis requires
(1) Energy, usually from the hydrolysis of ATP;
(2) Ca2+; and
(3) contractile elements in the cell (probably the
microfilament system)
Dr.N.Sivaranjani

Phagocytosis – cell eating
Occurs only in Macrophages and Granulocytes
Involves the ingestion of large particles such as viruses,
bacteria, cells, or debris
The particles are surrounded by pseudopodia to form
phagosomes.
Dr.N.Sivaranjani

Pinocytosis – cell drinking
is the property of the cells to uptake fluid and fluid
contents.
Two types :
a.) Fluid phase pinocytosis is non selective process of uptake
of fluid and its contents.
Formation of small vesicle is an active process.
Dr.N.Sivaranjani

Receptor Mediated Endocytosis / Absorptive Pinocytosis.
receptor-mediated selective process
Uptake of macromolecules for which there are a finite
number of binding sites on the plasma membrane
minimize the uptake of fluid or soluble unbound
macromolecules
vesicles formed are coated on the cytoplasmic side with a
filamentous material (protein clathrin ) – Coated pits
Clinical importance :-
Some viruses cause diseases by this mechanism
Hepatitis (affecting liver cells)
Poliomyelitis (affecting motor neurons)
AIDS Dr.N.Sivaranjani
(affecting T cells)

Receptor mediated absorptive pinocytosis
Eg: Low-density lipoprotein (LDL-C) and its receptor are
internalized by means of coated pits containing the LDL
receDpr.tN.oSivraranjani

Absorptive / selective Pinocytosis is receptor mediated.
Eg : LDL-C binds to LDL receptor
LDL receptor complex is internalized
cytoplasmic side of vesicles coated with Clathrin called as
Clathrin Coated pits
Coated vesicles fuse with endosomes
LDL-C is degraded by lysosomal enzymes
receptor molecules are release back to cell surface.
Dr.N.Sivaranjani

Membrane Channels and Pumps
Membrane is intrinsically impermeable to ions and polar
molecules
Permeability is conferred by
Channels
Pumps
Dr.N.Sivaranjani

Ion channels
Transmembrane
channels.
Pore like structures composed of proteins.
Transport Na+ K+ Ca++ and Cl- across the cell
membrane.
Ion channels have gates controlled by opening and
closing.
Dr.N.Sivaranjani

Ion channel are very selective, in most cases permitting
the passage of only one type of ion
Closed Open
Dr.N.Sivaranjani

Two types of gated channels :
a. Ligand gated channels – a specific molecule binds to a
receptor and opens the channels.
Eg. Acetyl chlorine receptor
b. Voltage gated channels – These channels open
(depolarization)or close (ground state) in response to the
changes in membrane potential.
Eg:- voltage gated Na+ channel & K+ channel
seen in nerve terminals & helps in nerve conduction .
Dr.N.Sivaranjani

Ionophores
Certain microbes synthesize small cyclic organic
molecules called ionophores.
Two major groups
– Mobile carriers (Valinomycin )
readily diffuse in a membrane & can carry an
K+ ion across a membrane
– Channel formers (Gramicidin )
create a channel that transverses the
membrane & through which ions can diffuse
Dr.N.Sivaranjani

Osmosis
The diffusion of water through a semi permeable
membrane.
Movement of water molecules occur from an area of lower
solute concentration to an area of higher solute
concentration.
Application of osmosis :
Fluid balance and blood volume
RBC and fragility
Diabetes Mellitus – Osmotic diuresis
Edema – hypoalbuminemia
Dr.N.Sivaranjani

Water channels (Aquaporins)
Membrane channel proteins that serve as selective pores
through which water cross the plasma membrane.
10 distinct Aquaporins (AP-1 to AP-10)
clinical aspects :
Nephrogenic Diabetes Insipidus – Mutations in the gene
encoding AP-2.
Water
molecules
Dr.N.Sivaranjani

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