The structure and function of
the plasma membrane
Learning objectives:
1. Model of membrane structure
2. Model of membrane structure: an experimental
perspective
3. The chemical composition of membranes
4. Characteristics of membrane
5. An overview of the functions of membranes
1.A brief history of studies on
plasma membrane structure
A. Concepts:
Plasma membrane(cell membrane),
Intracellular (cytoplasmic) membrane,
Biomembrane.
B. The history of study
”Overton(1890s):
Lipid nature of PM;
”Gorter and Grendel(1925):
The basis of membrane structure is a lipid bilayer
To answer the question that how many lipid layers were in
membrane, in 1925 Gorter and Grendel extracted the lipids
from a known number of erythrocytes and spread the lipid
film on a water surface. The area of lipid film on the water
was about twice(1.8-2.2) the estimated total surface area of the
erythrocytes, so they concluded that the erythrocyte plasma
membrane consisted of not one but two layers of lipids.
”H.Davson and J.Danielli(1935, 1954): “sandwich
model”
Membranes also contain proteins.
If the membranes only consist of pure lipids,
it could not explain all the properties of
membranes. For example, sugars, ions, and
other hydrophilic solutes move into and out
of cells much more readily than could be
explained by the permeability of pure lipid
bilayers. To explain such differences, Davson
and Danielli invoked the presence of proteins
in membranes in 1935.
The plasma membrane is composed of a
lipid bilayer that is lined on both its inner and
outer surface by a layer of globular proteins;
in addition to , the presence of protein-lined
pores for polar solutes and ions to enter and
exit the cell.
” J.D.Robertson(1959):
The TEM showing:the trilaminar
appearance of PM;
Unit membrane model;
” S.J.Singer and G.Nicolson(1972):
fluid-mosaic model;
Singer and Nicolson’s Model of membrane
structure: The fluid-mosaic model is the “central
dogma” of membrane biology.
A. The core lipid bilayer exists in a fluid state, capable
of dynamic movement.
B. Membrane proteins form a mosaic of particles
penetrating the lipid to varying degrees.
The Fluid Mosaic
Model, proposed in
1972 by Singer and
Nicolson, had two
key features, both
implied in its name.
Experimental evidence for the “mosaic” property of membranes
Freeze-fracture the membrane and observe protein “bumps”
” K.Simons et al (1997): lipid rafts model;
Functional rafts in Cell membranes.
Nature 387:569-572
Atomic force microscopy reveals sphyingomyelin rafts (orange) protruding from
a dioleoylphosphatidylcholine background (black) in a mica-supported lipid
bilayer. Placental alkaline phosphatase (yellow peaks), a
glycosylphosphatidylinositol-anchored protein, is shown to be almost
exclusively raft associated. [From D. E. Saslowsky et al., 2002, J. Biol. Chem.
277:26966–26970.]
2. The chemical composition of
membranes
z Membrane lipid: the lipid bilayer serves primarily
as a structural backbone of the membrane and provides
the barrier preventing the random movement of watersoluble materials into and out of cell.
z Membrane proteins: carry out most of the
specific functions
z Carbohydrates: have biological functions, such as
protection, recognition, adhesion
The basic compositions of some bio-membranes
Membrane
Plasma membrane
Red blood cell
Myelin membrane
Liver cell
Nucleus membrane
Golgi body
Endoplasmic reticulum
Mitochondrion
Outside membrane
Inside membrane
Chloroplast
Proteins (%)
Lipids (%)
Saccharide (%)
49
18
54
66
64
62
43
79
36
32
26
27
8
3
10
2
10
10
55
78
70
45
22
30
trace
-
A. Membrane Lipids: The Fluid Part of the Model
™Membrane lipids are amphipathic: hydrophilic & hydrophobic
™There are three major classes of membrane lipids:
z
Phospholipids:
Phosphoglyceride and sphingolipids
z Glycolipids
z Sterols ( is only found in animals)
Figure 10-2. The parts of a phospholipid molecule.
Phosphatidylcholine, represented schematically (A), in formula (B), as a
space-filling model (C), and as a symbol (D). The kink due to the cisdouble bond is exaggerated in these drawings for emphasis.
鞘氨醇
The class of
sphingolipids
神经酰胺
鞘磷脂
神经节苷脂
Effect of lipid composition on bilayer
thickness and curvature. (a) A pure
sphingomyelin (SM) bilayer is thicker than
one formed from a phosphoglyceride such
as phosphatidylcholine (PC). Cholesterol
has a lipid-ordering effect on
phosphoglyceride bilayers that increases
their thickness but does not affect the
thickness of the more ordered SM bilayer.
(b) Phospholipids such as PC have a
cylindrical shape and form more or less flat
monolayers, whereas those with smaller
head groups such as
phosphatidylethanolamine (PE) have a
conical shape. (c) A bilayer enriched with
PC in the exoplasmic leaflet and with PE in
the cytosolic face, as in many plasma
membranes, would have a natural
curvature. [Adapted from H. Sprong et al.,
2001, Nature Rev. Mol. Cell Biol. 2:504.]
Glycolipid molecules. Galactocerebroside (A) is called a neutral glycolipid because the
sugar that forms its head group is uncharged. A ganglioside (B) always contains one or more
negatively charged sialic acid residues (also called N-acetylneuraminic acid, or NANA), whose
structure is shown in (C). Whereas in bacteria and plants almost all glycolipids are derived from
glycerol, as are most phospholipids, in animal cells they are almost always produced from
sphingosine, an amino alcohol derived from serine, as is the case for the phospholipid
sphingomyelin. Gal = galactose; Glc = glucose, GalNAc = N-acetylgalactos-amine; these three
sugars are uncharged.
The structure of cholesterol. Cholesterol is represented by a formula in
(A), by a schematic drawing in (B), and as a space-filling model in (C).
The movement of membrane lipid
Four kinds of movement:
Lateral diffusion by
exchanging places;
Rotation around its long
axis;
Wave
Transverse diffusion, or
“flip-flop” from one
monolayer to the other.
Flippases catalyze the flipflop.
™The nature of the lipid bilayer: dynamic
z
z
The lipid bilayer is
deformable and their overall
shape can change, and
facilitate the fusion or budding
of membrane.
Self assemble (self-sealing):
the molecules of the lipid
bilayer can spontaneously
rearrange to eliminate a free
edge, such as a tear in the
bilayer.
amoeba
Nuclear transplantation
Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section.
Lipid molecules form such structures spontaneously in water. The shape
of the lipid molecule determines which of these structures is formed.
Wedge-shaped lipid molecules (above) form micelles, whereas cylindershaped phospholipid molecules (below) form bilayers.
Liposome: the phospholipid molecules assemble spontaneously in an
aqueous solution to form the walls of fluid-filled spherical vesicles
stealth liposome: study on nature; gene transfer; as a carrier.
B. Membrane carbohydrates
™Membrane contain carbohydrates covalently linked to lipids
and proteins on the extracellular surface of the bilayer.
™Glycoproteins have short , branched carbohydrates for
interactions with other cells and structures outside the cell.
™Proteoglycans have one or more long polysaccharide chains
™Glycolipids have larger carbohydrate chains that may be
cell-to-cell recognition sites.
™All of the carbohydrate on the glycoproteins, proteoglycans,
and glycolipids is located on one side of the membrane, the
noncytosolic side, where it forms a sugar coating called
glycocalyx.
™Functions of membrane carbohydrates
z The
glycocalyx helps to protect the cell
surface from mechanical and chemical
damage
z Membrane carbohydrate has an important
role in cell-cell recognition and adhesion
z The glycocalyx can serve as a kind of
distinctive clothing.
The blood type is
determined by a short
chain of sugars
covalently attached to
membrane lipids and
protein of the red blood
cell membrane
GalNAc: N-acetylgalactosamine
Gal: galactose
Glu: glucose
GlcNAc: N-acetylglucosamine
Fuc: fucose
C. Membrane Proteins
z
Integral proteins (intrinsic
membrane protein)
z
Peripheral proteins
(extrinsic membrane protein)
z
Lipid-anchored proteins
According to the intimacy of
membrane proteins’ relationship to
the lipid bilayer
A polypeptide chain usually crosses
the bilayer as an α helix
Peripheral proteins
z
They associated with the
membrane by weak
electrostatic bonds either
to the hydrophilic head
group of lipids or to the
hydrophilic portions of
integral proteins
protruding from the
bilayer
z
They can be solubilized by extraction with aqueous salt
solutions (i.e. by changing ionic strength, pH, etc.)
The peripheral proteins located on the internal surface of the
plasma membrane form a fibrillar network that acts as a
membrane skeleton
(spectrin, band 3, glycophorin A)
z
Lipid-anchored proteins
z
z
GPI-anchored proteins:
present on the external face
of the plasma membrane and
bind to the membrane by a
short oligosaccharide linked
to a molecule of GPI
(anemia: paroxysmal
nocturnal hemoglobinuria)
GPI: glycosylphosphatidylinositol
Another group of proteins present on the cytoplasmic side
of the membrane and linked to the membrane by long
hydrocarbon chains embedded in the inner leaflet of the
lipid bilayer
™The orientation of integral proteins can be
determined using nonpenetrating agents that label
the proteins.
SDS-polyacrylamide gel electrophoresis (SDS PAGE)
Radioactive isotope: I
lactoperoxidase
™ Detergents
Integral proteins are embedded in the membrane;
their removal requires detergents.
z Detergents:
small, amphipathic
z Sodium dodecyl sulfate (SDS): strong ionic
detergent CH3-(CH2)11-OSO3-Na+
z Triton
X-100: a mild nonionic detergent
CH3
CH
CH3 – C – CH2 – C –
CH3
CH3
(O-CH2-CH2)10- OH
Membrane Proteins:
The “Mosaic” Part of the Model
™Membranes contain integral, peripheral, and
lipid-anchored proteins:
lipid-anchored proteins
Rolled-up β sheet
α helix
Amphipathic α helix
Noncovalent interactions
3. the fluidity of lipid membranes
z Fluidity: the degree of movement of lipid molecules in
the plane of lipid membrane
z State:
liquid crystalline phase
frozen crystalline gel phase
z Influential elements of fluidity:
temperature (transition temperature)
phospholipid composition (the length and
unsaturation of the hydrocarbon tails; cholesterol)
z
z
a) above the transition temperature, the lipid molecules and
their hydrophobic tails are free to move in certain direction,
even though they retain a considerable degree of order
b) below the transition temperature, the movement of
molecules is greatly restricted, and the entire bilayer can be
described as a crystalline gel.
Figure 10-7. Influence of cis-double bonds in hydrocarbon chains.
The double bonds make it more difficult to pack the chains together and
therefore make the lipid bilayer more difficult to freeze.
z
Cholesterol stiffens the bilayer and makes it less
fluid and less permeable (cholesterol-sphingolipid patches
have higher transition temperature than that of surrounding
phospholipids); interfere with the tight packing of the
phospholipids, which tends to increase the fluidity of the
bilayer.
4. The asymmetry of membrane
™ The asymmetry of membrane lipids and glycolipids :
The inner and outer membrane leaflets were shown to
have different lipid compositions.
™ Lipid asymmetry gives the
membrane leaflets different
physical and chemical
properties appropriate for the
different interactions occurring
at the two membrane faces.
The asymmetric distribution of
Phospholipid in Human Erythrocytes
™The asymmetry of membrane protein
and glycoprotein :
ƒIntegral proteins attach to the bilayer asymmetrically, giving
the membrane a distinct “sidedness”.
ƒThe membrane carbohydrates only distributing on
extracellular side (more precisely, noncytosolic side).
ƒ Integral proteins have orientation within Membranes.
ƒ The distribution of
integral proteins can
be analyzed by
freeze-fracture and
freeze-etching
techniques.
ES (extrocytoplasmic surface)；PS:（protoplasmic surface)；
EF（extrocytoplasmic face）；PF（protoplasmic face）
The inhomogeneity of membranes
™ Lipid composition can influence the activity of
membrane proteins and determine the physical state
of the membrane.
™Biomembrane have agglomeration
Model of
Lipid raft in
TGN
Patterns of movement of integral membrane proteins
membrane proteins move
randomly throughout the
membrane, though generally at
rates considerably less than
would be measured in an
artificial lipid bilayer (A).
z Some membrane proteins fail to
move and are considered to be
immobilized(B).
z a particular species of proteins
is found to move in a highly
directed manner toward one part
of the cell or another (C).
z
Movement of protein D is restricted by other integral protein; movement of protein E
Is restricted by fences formed by proteins of the membrane skeleton; movement of
Protein F is restrained by extracellular materials.
The lateral diffusion of membrane proteins can demonstrated
experimentally by a technique called Fluorescence Recovery
After Photobleaching (FRAP).
Many membrane proteins vary in their mobility.
Protein movements are limited by interactions with
the cytoskelton, other proteins, and ECM.
The mobility of membrane proteins can be shown experimentally by the
mixing of membrane proteins that occurs when two cells are tagged with
different fluorescent labels and then induced to fuse.
Figure 10-37. Diagram of an epithelial cell showing how a plasma
membrane protein is restricted to a particular domain of the
membrane. Protein A (in the apical membrane) and protein B (in the basal and
lateral membranes) can diffuse laterally in their own domains but are prevented from
entering the other domain, at least partly by the specialized cell junction called a tight
junction. Lipid molecules in the outer (noncytoplasmic) monolayer of the plasma
membrane are likewise unable to diffuse between the two domains; lipids in the inner
(cytoplasmic) monolayer, however, are able to do so.
Figure 10-38. Three
domains in the plasma
membrane of guinea pig
sperm defined with
monoclonal antibodies. A
guinea pig sperm is shown
schematically in (A), while each
of the three pairs of micrographs
shown in (B), (C), and (D)
shows cell-surface
immunofluorescence staining
with a different monoclonal
antibody (on the right) next to a
phase-contrast micrograph (on
the left) of the same cell. The
antibody shown in (B) labels
only the anterior head, that in (C)
only the posterior head, whereas
that in (D) labels only the tail.
(Courtesy of Selena Carroll and
Diana Myles.)
Figure 10-39. Four ways in
which the lateral mobility
of specific plasma
membrane proteins can be
restricted. The proteins can
self-assemble into large
aggregates (such as
bacteriorhodopsin in the purple
membrane of Halobacterium) (A);
they can be tethered by
interactions with assemblies of
macromolecules outside (B) or
inside (C) the cell; or they can
interact with proteins on the
surface of another cell (D).
Figure 10-22. A scanning electron micrograph of human red blood
cells. The cells have a biconcave shape and lack nuclei. (Courtesy of
Bernadette Chailley.)
Figure 10-24. SDS polyacrylamidegel electrophoresis pattern of the
proteins in the human red blood
cell membrane. The gel in (A) is
stained with Coomassie blue. The
positions of some of the major
proteins in the gel are indicated in the
drawing in (B); glycophorin is shown
in red to distinguish it from band 3.
Other bands in the gel are omitted
from the drawing. The large amount
of carbohydrate in glycophorin
molecules slows their migration so
that they run almost as slowly as the
much larger band 3 molecules. (A,
courtesy of Ted Steck.)
Figure 10-26. The spectrin-based cytoskeleton on the cytoplasmic side of the
human red blood cell membrane. The structure is shown schematically in (A) and in an
electron micrograph in (B). The arrangement shown in (A) has been deduced mainly from studies
on the interactions of purified proteins in vitro. Spectrin dimers associate head-to-head to form
tetramers that are linked together into a netlike meshwork by junctional complexes composed of
short actin filaments (containing 13 actin monomers), tropomyosin, which probably determines
the length of the actin filaments, band 4.1, and adducin. The cytoskeleton is linked to the
membrane by the indirect binding of spectrin tetramers to some band 3 proteins via ankyrin
molecules, as well as by the binding of band 4.1 proteins to both band 3 and glycophorin (not
shown). The electron micrograph in (B) shows the cytoskeleton on the cytoplasmic side of a red
blood cell membrane after fixation and negative staining. (B, courtesy of T. Byers and D. Branton,
PNSA. 82:6153-6157)
An overview of membrane functions
1. Define the
boundaries of the cell
and its organelles.
2. Serve as loci for
specific functions.
3. provide for and
regulate transport
processes.
4. contain the receptors
needed to detect
external signals.
5. provide mechanisms
for cell-to-cell contact,
communication and
adhesion
A. PM define the boundaries of the cell and
organelles.
B. Compartmentalization: membranes form
continuous sheets that enclose intracellular
compartments.
C. Transporting solutes: membrane proteins
facilitate the movement of substances between
compartments.
D. Responding to external signals: membrane
receptors transduce signals from outside the
cell in response to specific ligands.
E. Intercellular interaction: membrane
mediate recognition and interaction between
adjacent cells by cell-to-cell communication
and junction.
F. Locus for biochemical activities: membrane
provide a scaffold that organizes enzymes for
effective interaction.
G. Energy transduction: membranes
transduce photosynthetic energy, convert
chemical energy to ATP, and store energy in
ion and solute gradients.
Analysis of membrane proteins by using of
molecule biological technique
Questions
z What
is the fluid-mosaic model of the
plasma membrane?
z How to understand the fluidity of lipid
membranes?
z What leads to the asymmetry of lipid
membranes?