Phospholipids form the basic structure of a cell membrane, called the lipid bilayer. Scattered in the lipid bilayer are cholesterol molecules, which help to keep the membrane fluid consistent. Membrane proteins are important for transporting substances across the cell membrane.

1. Physiochemical principles
Senior Lecturer

2. Structure of cell membrane
Fluid mosaic model
 Fluid mosaic model was discovered by S. J. Singer and
G. L. Nicolson in 1972.
 This model explains well the architecture of cell
membrane.

3.  Biological membranes can be considered as a two
dimensional liquid in which lipid and protein
molecules diffuse more or less easily.

5. Lipid bilayer
 Cell membrane is a lipid bilayer structure.
 Phospholipids form a bilayer in which the nonpolar
regions (tails) of the lipid molecules in each layer face the
core of the bilayer.

6.  And their polar head groups face outward, interacting
with the aqueous phase on either side.

8.  In the lipid bilayer, proteins are embedded at irregular
intervals.
 These proteins are held in place by hydrophobic
interactions between them and the membrane lipids.
 Some proteins span the whole thickness of the membrane.

9.  While others span partially, protruding either on the
exterior or the interior of the cell membrane.

10.  The orientation of proteins in the bilayer is
asymmetric, giving the membrane “sidedness”: the
protein domains exposed on one side of the bilayer are
different from those exposed on the other side, reflecting
functional asymmetry.

11.  The irregular distribution of proteins in the lipid bilayer
gives it the so called mosaic appearance.
 However, the mosaic is not constant but is fluid, i.e.
changeable from moment to moment.

12. The fluidity of the mosaic is due to weak (non-covalent)
interactions between lipid and protein molecules that
enable individual lipid and protein molecules to move free
laterally in the plane of the membrane.

13. A lipid bilayer is the basic structural element of
membranes
 Lipids (glycerophospholipids, sphingolipids, and sterols)
are virtually insoluble in water. When mixed with water,
they spontaneously form microscopic lipid aggregates.

14.  Depending on the precise conditions and the nature of the
lipids, three types of lipid aggregate can form when
amphipathic lipids (all lipids in membrane because they
have hydrophilic and the hydrophobic end) are mixed with
water.

15.  These are:
a. Micelle
b. Bilayer
c. Vesicle

16. a. Micelle
 Micelles are spherical structures that contain anywhere
from a few dozen to a few thousand amphipathic
molecules.

17.  These molecules are arranged
with their hydrophobic
regions aggregated in the
interior, where water is
excluded.

18.  And their hydrophilic head groups at the surface are in contact
with water.
 Micelle formation is favored when the cross-sectional area of the
head group is greater than that of the acyl side chain(s), as in
detergents such as sodium dodecyl sulfate.

19. b. Bilayer
 A second type of lipid aggregate in water is the bilayer, in
which two lipid monolayers (leaflets) form a two
dimensional sheet.
 The hydrophobic portions in each monolayer is excluded
from water and interact with each other.

20.  The hydrophilic head groups
interact with water at each
surface of the bilayer.

21.  Bilayer formation is favored if the cross-sectional areas of
the head group and acyl side chain(s) are similar, as in
glycerophospholipids and sphingolipids.

22. c. Vesicle
 The bilayer sheet is relatively unstable and spontaneously
folds back on itself to form a hollow sphere that is called
a vesicle because the hydrophobic regions at its edges are
in contact with water.

23.  The continuous surface of
vesicles eliminates the
exposed hydrophobic regions,
allowing bilayers to achieve
maximal stability in their
aqueous environment.

24.  Vesicle formation also creates a separate aqueous
compartment.

25. Membrane proteins
 There are three types of membrane proteins that differ in
their association with the membrane.
1. Integral membrane proteins
2. Peripheral membrane proteins
3. Amphitropic proteins

27. 1. Integral membrane proteins
 Integral membrane proteins or intrinsic proteins are very
firmly associated with the lipid bilayer, and are removable
only by agents that interfere with hydrophobic
interactions, such as detergents, organic solvents, or
denaturants.

28. 2. Peripheral membrane proteins
 Peripheral membrane proteins or extrinsic proteins
associate with the membrane through electrostatic
interactions and hydrogen bonding with the
hydrophilic domains of integral proteins and with the
polar head groups of membrane lipids.

29. '
 They can be released by relatively mild treatments that
interfere with electrostatic interactions or break hydrogen
bonds; a commonly used agent is carbonate at high pH.

30. 3. Amphitropic proteins
 Amphitropic proteins are found both in the cytosol and in
association with membranes.
 These are sometime attach with membranes and
sometimes not depending on some type of regulatory
process such as reversible palmitoylation.
 Their affinity for membranes results in some cases from

31.  And in other cases from the presence of one or more
lipids covalently attached to the amphitropic protein.