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CELL MEMBRANE ( www.cmbio.blogfa.

com )

1. Properties of cell membrane


2. Chemistry structures of membrane lipids
3. Fluid-mosaic model of plasma
membrane
4. Clinical manifestations on the basis of
certain membrane dysfunctions

Prof. K.M. Chan, Biochemistry, Rm513B, BMSB.


Email: kingchan@cuhk.edu.hk; Tel: 3163-4420.
Lipids are water insoluble
and amphipathic in nature.
hydrophobic
hydrophilic
A liposome
formed with water
lipid bilayer: Lipid on the
surface of water

Bubbles with soap trapping a layer


of water inside; with the detergents
Lipid at the outside (just the reverse of
bilayer the lipid bilayer of plasma
membrane).
hydrophobic
hydrophilic

hydrophilic
water water hydrophobic
1. Properties of plasma membrane

 Sheet-like (layer) structure consists of proteins, lipids,


with carbohydrates attached to proteins or lipids outside
of the membrane.
 Non-covalent assemblies of lipids and proteins.
 The lipid molecules are amphi-pathic molecules, they
have both hydrophilic (polar) and hydrophobic (non-
polar) moieties.
 Barriers to the flow of charged molecules and large
molecules. Mainly hydrophobic or lipid soluble
molecules can go through.
 Transmembrane proteins serve as transporters,
channels, enzymes, signal transducers, etc.
1.1 Plasma membranes
 Membranes are held up with van der Waal’s force and
hydrophobic interaction with no covalent interactions
among molecules, therefore they can fuse together and
break up by hydrophobic interactions. These membrane
fusion processes are mainly controlled by peripheral
proteins underneath the membrane.
 Budding, endocytosis and exocytosis are common
membrane movements by membrane fusion.
 By membrane fusion, Golgi complex and move proteins
to vesicles and surface membrane. Secretory proteins
can be bound with vesicles and released out of the
cells.
 The mitochondrion has 2 layers of membrane, the inner
is similar to their descendant of prokaryotes, the outer
from eukaryotes; indicating its symbiotic origin.
1.2 Fatty acids and phospholipids
 Membranes have three kinds of lipids:
phospholipids, glycolipids, & cholesterol
 Fatty acids (FAs) form the basic structures of
phospholipids and glycolipids
 Saturated FAs VS Unsaturated FAs
 Strong van der waals interaction between the
non-polar hydrocarbon regions of the molecules
Common saturated fatty acids
Structure
Common Systematic
Abbreviation Hydrophobic hydrocarbon
Name Name
(alipathic) tail
Capric n-Decanoic 10:0 CH3(CH2)8COOH

Lauric n-Dodecanoic 12:0 CH3(CH2)10COOH

Myristic n-Tetradecanoic 14:0 CH3(CH2)12COOH

Palmitic n-Hexadecanoic 16:0 CH3(CH2)14COOH

Stearic n-Octadecanoic 18:0 CH3(CH2)16COOH

Arachidic n-Eicosanoic 20:0 CH3(CH2)18COOH

Behenic n-Docosanoic 22:0 CH3(CH2)20COOH

Lignoceric n-Tetracosanoic 24:0 CH3(CH2)22COOH

Cerotic n-Hexacosanoic 26:0 CH3(CH2)24COOH


Common unsaturated fatty acids
Common Systematic Structure
Abbreviation
Name Name Hydrophobic hydrocarbon (alipathic) tail
cis-9-
Palmitoleic 16:1c∆9 CH3(CH2)5CH=CH(CH2)7COOH
Hexadecenoic
cis-9-
Oleic 18:1c∆9 CH3(CH2)7CH=CH(CH2)7COOH
Octadecenoic
Cis,cis-9,12-
Linoleic 18:2c∆9,12 CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
Octadecadienoic
All-cis-9,12,15- CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7C
Linolenic 18:3c∆9,12,15
Octadecadienoic OOH
All-cis-5,8,11,14- 20:4c∆ CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2C
Arachidonic
Eicosatetraenoic 5,8,11,14 H=CH(CH2)3COOH
Melting points of saturated fatty acids increase with increasing molecular
weight; melting points of unsaturated fatty acids are determined by the
number of double bonds (cis C=C bonds rotate 120 O).

Changes from a gel state to a liquid


state at special melting temperature
90
20
Melting Point ºC

Melting Point ºC
80
10
70

60 0
The melting points of
saturated fatty acid
50 increase with -10
increasing molecular
40 weight -20
30
8 10 12 14 18 22 26 28 1 2 3 4

Number of carbon Number of double bonds


1.3 structure of lipid bilayer and
phospholipids
Fatty acids (FAs) form the
Phospholipid molecule
basic structures of
Hydrophili phospholipids
c head on
Polar group
Hydrophilic surface
head Phosphat
e

Hydrophobic core
Glycerol

of lipid bilayer
Hydrophobi
c fatty acid Fatty acid-
tails (unsaturate
d)

Fatty acid Hydrophilic head to cytoplasm


(saturated)
Lipid bilayer at work: [1] melting points affect the
fluidity, [2] hydrophobic actions form the membrane.

Tightly packed: more


Loosely packed:
rigid and lower higher fluidity
fluidity

Increase of
temperatur
e

Explain why and how a detergent can kill


germs?? Why bleach and alcohol can kill
bacteria and viruses??
2. Chemical Structures of Membrane lipids

Comparison of storage lipids (neutral) and membrane lipids (polar) with


Glycerophospholipids and Sphingolipids (including glycolipids)
POLAR MEMBRANE LIPIDS
Triacylglycerols, Phospholipids: Glycolipids:
Phospholipids:
storage lipids Glycero-
Shingolipids Shingolipids
(neutral) phospholipids (neutral)

Polysaccharide
Fatty acid Phosphate Sphingosine

Glycerol Polar head


group Monosaccharide

Adapted from Nelson and Cox, 2000. Lehninger Principles of Biochemistry. Worth Pub.Co.
2.1 Glycerophospholipids
and sphingolipids
 Different ways of putting two fatty acid chains
together as major phospholipids on membrane
 Glycerophospholipids with GLYCEROL
linkage, e.g. phosphatidyl choline or serine.
 Sphingolipids are derived from sphingosine,
e.g. sphingomyelin, which has no glycerol
linkage.

Glycero-phospholipids Shingolipids
2.2 Sphingomyelins, forming a ceramide first
by adding a fatty acid chain, e.g. Sphingolipid
as a major component of nerve cells

Sphingosine
2.3Glycolipids: Cerebrosides
(e.g. Sphinoglycolipids)

Ceramide
Gangliosides: 6% of brain lipids, ceramide
oligosaccharides with sialic acid residue(s),
excellent for recognition by antibodies.
2.4 Cholesterol stays in between fatty acids with its
rigid planar steroid ring and affect membrane fluidity

Polar Head

Polar Head Phosphat


e
Glycerol

Fatty acid-
(unsaturate
d)
Hydrophobi
c fatty acid
tails

Non polar
hydrocarbon
Tail

Bacterial cells do not have cholesterol, neither in


mitochondria too.
3. The Fluid-Mosaic Model
(Singer and Nicolson, 1972):

• Amphipathic lipids form a bilayer stabilized by the


hydrophobic interaction.
• The lipid bilayer is a fluid-like structure, with
fluidity regulated by the number of double
bonds in the fatty acids (increasing unsaturation
increases fluidity) and cholesterol content
(increasing cholesterol decreases fluidity).
• The components of membranes with lipids and
proteins are asymmetrically oriented: the two
faces are different.
3.1 The Fluid-Mosaic Model (cont’)
4. The proteins and the components are
free to move laterally (lateral movement
allowed), but no or little flip-flopping
allowed (flippase or transporter is needed.
 The lipid bilayer forms a permeability
barrier to polar molecules which can only
cross the membrane by a specific method
via membrane proteins: permeases,
channel, or transporters)
 Clustering, capping of lipids or proteins on
cell surface also exist (not really random)
3.2 The asymmetrical nature of plasma membrane: polar
heads of phospholipids and carbohydrates of glycolipids
vary on two sides of the lipid bilayer; protein orientations
also vary and are fixed too.
carbohydrates

Cell Wall

Rotations
Lipid occur
bilayer Peripheral Integrated Protein (NO
proteins flip-flopping)

Cytoskeleton below may


control these trans-
membrane proteins
Lateral transport modes on the cell surface: A. Transient
confinement by Obstacle clusters; B. by Cytoskeleton; C.
Directed motion; D. Random Diffusion.

B D
A

Lipid C
raft
exists

Adapted from Jacobson et al, 1995, Revisiting the fluid mosaic model
of membranes. Science 268:1441-1442.
3.4 Possible ways of proteins stay
with the plasma membrane
(1)Trans-membrane (2) Lipoproteins (3) Protein attached
N
C C C
C
C

Lipid
βbarrel N
N bilayer
N
C
Trans-membrane proteins N
N
must have hydrophobic C
region, usually helical N
bundles, to get into the
membrane’s core
hydrophobic region: Adapted from Alberts et al., 1998. Essential Cell
hydrophobic interactions. Biology. An Introduction Biology of the Cell.
Garland Pub.Inc.
4. Clinical Correlations
 Snake venom contains phospo-lipase which
removes fatty acid from phosphatidylcholine on
membrane, causing hemolysis of red cells to leak red
cell contents into the plasma and leading to blood
clotting and swollen of limbs (edema).
 Ankyrin and or spectrin deficiency can cause
anemia. Red cells are disrupted without the peripheral
proteins to hold the membrane.
 Human Immunodeficiency Virus enters the cells like
other viruses on their specific cell surface proteins.
HIV binds gp120 , with CD4 and CCR5, on the target
T cell.
 Membrane consists of amphipathic compounds, many
drugs or toxins (e.g. antibiotics) are amphipathic
compounds to perturb membrane structure and work
as detergent to disrupt or break-up the lipid bilayer.
Final remarks:
 Chemical properties of fatty acids are essential to the
structure and function of plasma membranes.
 Cholesterol and fatty acid composition are key
fluidity regulator of cell membrane.
 Fluid-mosaic model of membrane is well established:
proteins embedded in lipid bilayer. Orientations of the
membrane is fixed, no flip-flopping.
 Proteins are responsible for most if not all the major
cellular functions (homeostasis) of cell membranes.
 Integral proteins get into the cell membrane with their
hydrophobic transmembrane domains which consist
of helical bundles spanning through the membrane.
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