Bhaskar Ganguly

Ph.D. , M.V.Sc. , B.V.Sc. & A.H.

 Overton {1890s}:
Lipids are present on cell surfaces; cell coats are probably mixtures
of cholesterol & lecithin

Langmuir {1900s}:
Phospholipid monolayer

Gorter & Grendel {1925}:

Lipid Bilayer

 Davson & Danielli {1935}:

Biological membranes consist of lipid bilayers coated on both sides
by thin sheets of proteins

Robertson {1960}:
All cellular membranes share a common underlying structure viz.
Unit Membrane

 Singer & Nicolson {1972}:

Biological membranes consist of a mosaic of proteins in a lipid
bilayer; The Fluid-Mosaic Model

 Behavior of lipid matrix depends on the properties of

individual lipid components

Lipid matrix interacts with proteins and influences activity of

the proteins
Depending on duration of interactions, lipids are classified as

Restricted lipids: long residence time, slow exchange with

surrounding lipids
Interfacial lipids: form coat or ring around the circumference
of proteins, exchange rapidly with surrounding lipids
Restricted and Interfacial lipids may be necessary for protein
function

 Form structural and environmental framework for cell function

Phosphatidylcholine (PC), phosphatidylserine (PS) &
phosphatidylinositol (PI): provide hydrated or charged
membrane surfaces, allowing water/ ions to bind
Phosphatidylethanolamine (PE): hydrophobic, promotes
surface interactions without protein-protein interactions,
promotes formation of non-bilayer structures; necessary for
membrane fusion
Asymmetrical distribution between inner and outer leaflets
Outer leaflet: rich in PC & sphingomyelin
Inner leaflet: rich in PE & PS
Asymmetrical distribution is achieved & maintained by ATPdependent Aminophospholipid Translocase; translocates PE &
PS between leaflets

Differential distribution of lipids in leaflets

Per cent distribution of phospholipids in erythrocyte membrane

Role of translocases/ flippases in maintaining membrane asymmetry

 Reduces freedom of movement of phospholipids, rigidifying

effect on membrane viz. Condensing effect
Non-uniform distribution in different cell membranes
Decreases fluidity at high temperatures; increases fluidity at
low temperatures
Decreases permeability to ions & small polar molecules

At low temperatures, cholesterol disallows close packing of hydrocarbon chains; at high

temperatures, the rigid molecule restricts freedom of the acyl chains

 A state of change achieved by the motions of individual

membrane components & their interrelationships in nonrepeating units of the membrane
Asymmetric distribution of different lipids adds another
dimension to Membrane Dynamics
Re-distribution (lateral &/ or transverse) influences membrane
properties, and allows differential regulation of membrane
proteins
Biological case studies:

PLATELETS, &
PHOTORECEPTORS

 PC & Sphingomyelin in
outer leaflet; PE & PS in
inner leaflet
Cholesterol : Phospholipid
0.50
Platelets cannot synthesize
cholesterol; derived from
megakaryocyte progenitor

(%) lipids in plasma membrane

PC

PE

PI

PS

Sphingomyelin

Membrane cholesterol concentration represents plasma

cholesterol concentration
Membrane cholesterol is also acquired from plasma
lipoproteins

 Upon stimulus for aggregation, asymmetry of phospholipid

distribution is lost

PE is rapidly translocated from inner to outer leaflet

Aminophospholipid translocase is not inhibited; instead,
Scramblase is involved (induced by high intracellular Ca++)
Cholesterol translocates from outer to inner leaflet;
thermodynamic exclusion of cholesterol due to unfavorable
entropy of co-existence with PE
Higher cholesterol results in stronger response to stimulus
High membrane cholesterol platelets are more sensitive to
epinephrine, ADP, collagen & thromboxane A2
Cholesterol enrichment increases signaling events viz. release
of arachidonic acid, increased adrenergic & thrombin
receptors, and higher Ca++ & inositol phosphate levels

 Cholesterol behaves both as a restricted and interfacial lipid

Platelet stimulation increases rigidity & decrease fluidity
Activation of platelets alters platelet membrane to create a
catalytic site for conversion of factor X to factor X-a, and of
prothrombin to thrombin, leading to fibrinogen formation

Creation of catalytic site requires surfacing of PS from the

inner leaflet

Rod Outer Segment

(ROS)

Plasma
Membrane

Disk

Biochemical events initiating the impulse occur in membranous

sacs called disks in the ROS
New disks form from the ROS plasma membrane; old disks
displaced apically are shed off & phagocytosed by retinal
epithelium ( 10 days)

 Disks & Plasma membranes differ

in lipid composition
Plasma membrane: richer in
cholesterol & squalene (sterol
precursor),
PE:PC
=
0.16,
docosahexaenoic acid (DHA) ~5 %
Disks: PE:PC = 0.92, DHA ~ 35 %

11-cis retinal
all trans retinal

Rhodopsin
Metarhodopsin I
Metarhodopsin II

Metarhodopsin II
Transducin
cGMP dependent
Phosphodiesterase (PDEase)

Basal disk ~ 30 mol% cholesterol, apical disk ~ 5 mol%; same

mechanism as platelets (exclusion from PE-rich disk membrane)
Cholesterol influences rhodopsin function; cholesterol inhibits
activation of PDEase by rhodopsin
Conversion of Metarhodopsin I to larger Metarhodopsin II
requires kinking of unsaturated acyl chains; cholesterol resists
these free volume changes

 Cholesterol also interacts directly with rhodopsin

DHA influences regeneration of rhodopsin

DHA can contribute as six cis- bonds; cis- bonds increase
kinking within membrane bilayer thereby increasing free
volume
Rhodopsin is maintained in a relatively inactive state in plasma
membrane; cholesterol (= inhibition of activation), DHA (=
slow regeneration), i.e., Cholesterol/DHA favors inactivity
In disk membrane, Cholesterol/DHA favors rapid activation
and regeneration necessary for proper vision

http://sites.google.com/site/vetbhaskar