The plasma membrane

(structure)
RB.Soeherman H,dr.,MKes

LEARNING OBJECTIVES

At the end of this lecture, the students should be able to describe the structure of
the plasma membrane.
References:
- Steven R-Goodman : Medical Cell Biology,second ed. 1998
- Lodish, H. :et.al. : Molecular Cell Biology. Third ed. 1995
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The Membrane Structure

The basic structure of biologic membrane s is
a lipid bilayer,in which the polar head group of
the PL face the water and the hydrocarbon fatty
acid tails face the hydrophobic core.
Basic structure:lipid bilayer
*phospholipid : 50%
*protein
*carbohydrate
*cholesterol
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General architecture of lipid membranes

*The cellular plasma and organelle
membranes within the body contain 40%80% lipid the most prevalent
:phospholipid.
*4 mayor phospholipids in human and animal
membranes are:
-Phosphatidyl Choline(PC) polar head group
choline
-Phosphatidyl Serine (PS) serine
-Phosphatidyl Etanolamine(PE) etanol
amine
-Phosphatidyl Inositol(PI) inositol
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The polar head group for the phospholipids can

be either choline,serine,ethanol amine or inositol,
linked by a phosphate ester bond to carbon 3 of the
glycerol backbone, where as the hydrophobic
portion of the phospholipids contain 2
hydrocarbon fattyacyl chains linked to carbons 1
and 2 of the glycerol backbone.
In human and animal,the cellular plasma
membranes,the phospholipids contain fatty acids
that typically contain an number of carbon atoms
(16,18,or 20),and one of the fatty acids is
unsaturated(contains at least 1double bond).

The structure of phosphatidyl choline and spingomyelin-----both have a choline-containing polar head group and non polar hydrocarbon
tails
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The saturated fatty acid is straight and

flexible,where as the unsaturated fatty acid has a
rigid kink at the site of double bond.

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The hydrophobic effect acting on phosphatidyl

choline,,PS,PE,PI and SM,when an aqueous solution,
will result in a bilayer with polar head groups facing
the water and fatty acyl tails forming a hydrophobic
core.The fatty acyl tails also interact with each other
by weak van der Waals contacts.
At neutral pH ,only PS contains a net negative
charge.
Various biological membranes differ in their
absolute phospholipid composition,but all form the
lipid bilayer.(tab 2-1)

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Tab 2-1

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GLYCOLIPIDS

Lipids with attached sugar residues

minor components of membrane
the sugar residues of plasma membrane glycolipid
almost always face the outside of the cell,and have an
asymmetric distribution,found only in outer leaflet of
the bilayer.
-produced primarily from ceramide
-are referred to as glycosphingolipids

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cell membranes contain neutral glicolipid:with 1-15

uncharged sugar residues and gangliosides with 1 or more
negatively charged sialic acid sugars.
important in cell-cell interactions and cell-interstitial
matrix interactions, contribute to the negative charge of
the cell surface, and play a role in immune reactions.

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Glycoproteins and Glycolipid

-Carbohydrates found in many membranes:
covalently bound either to protein glyco
protein or to lipid glycolipid.
-abundant in the plasma membrane of eukaryo
tic cells,but are abscent in:inner mitochondrial
membrane,chloroplast lamellae, etc
Function:
-Increase the hydrophilic character of lipids
and proteins.
-Stabilize the membrane protein.
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Carbohydrate components are

oligosacharides:
- Galactose,
- Mannose,
N.acethylneuraminic(sialicacid),
-N.acethylgalactosamine,
- N.acethyl glucosamine,
- Fucose.

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Glycolipids :located in the cell surface membrane.

Glucosyl cerebroside:the simplest glycolipid,contain

a single glucose unit attached to a ceramide.
Gangliossides:glycolipids containing sugar
residue:N-acetyl neuraminic acid,and are abundant in
the plasma membrane of nerve cells and other
mammalian cells.
Glycolipids are always found in the exoplasmic
leaflet of membranes.

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-Glycoproteins or glycolipids present on the

surface of erythrocytes and other type cells
blood
group A, B, AB and O.
Blood group antigens can trigger immune
reaction
-CH portion in GL or GP Antigenic determinant
genetically determined
-All people have enzymes that synthesize
the O antigen.
-The O antigen is a chain of fucose, galactose,
glucose and N.acethylglucosamine.
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The A antigen is similar to O, except that the A antigen

contains an N-acetylgalactosamine attached to the outer
galactose residue;
the B antigen is also similar to O, except for an extra
galactose residue attached to the outer galactose.
All people have the enzymes that synthesize the O
antigen. People with type A blood also have the enzyme
that adds the extra N-acetylgalactosamine; those with type
B blood have the enzyme that adds the extra galactose.
People with type AB blood synthesize A and B antigens;
those with type O make only the O antigen.
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As shown in Table 14-3, people who cannot

synthesize the A and/or B antigen normally
have antibodies against the antigen(s) in their
serum.
Thus, when type B or AB blood is transfused
into a person with blood type A or O, the anti-B
antibodies of the recipient bind to the
transfused erytrocytes and trigger their
destruction by phagocytic cells.
Similarly, type A or AB blood cannot be
safely transfused into people with blood type B
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People with blood type AB, who lack both

anti-A and anti-B antibodies, can receive
blood of any ABO type.
People with type O blood can only be
transfused with type O blood, since they
have both anti-A and anti-B antibodies;
however, type O people are universal
donors, because their blood lacks both the
A and B antigen and can thus be transfused
into individuals of any ABO type.
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Membrane Protein
The Function:
-Cytoskeleton
-Transportation
-Receptor
-Brush border
-Filter and many specific function.

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PROTEINS
Responsible for membrane funtions
Transport of ions and polars molecules
Binding of hormones
Signal transduction across the membrane,
Structural stabilization of the bilayer
The protein:lipid ratio in biological membrane varies
substantionally correlates with the degree of
membrane funtion.
in Myelin:protein lipid ratio:0.23 serves as an
insulator of axons
Mitochondrial inner membrane:3.2 responsible
for electrone transport and oxidative
phosphorilation(fig 2-4)
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Fig 2-4 The protein :lipid ratio

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Membrane Organization
-All integral proteins bind asymetrically to the lipid bilayer.
-Integral protein single, spesific orientation
to cytosolic and exoplasmic faces.
-The two membrane leaflets have different lipid
compositions.
-Lipid with neutral or negative polar head groups located
in cytoplasmic leaflet:phospatidyl etanolamine,P.serine
-Glycolipid are always found in exoplasmic
leaflet.
-Integral proteins and lipids are mobile
-Some protein interact with cytoskeletal compound.
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Membrane protein: 2 basic type: integral and

periferal
INTEGRAL MEMBRANE PROTEIN (IMP)
-Embedded in the lipid bilayer and cannot be
removed without disrupting the lipid bilayer.
PERIPHERAL MEMBRANE PROTEIN(PMP)
-proteins that can be removed from membrane
without dissolving the bilayer.
-remove by shifting the ionic strength or pH of the
aqueous solution causing dissociation of the
ionic interactions of the peripheral protein with
either phospholipid polar head groups or other
membrane proteins.
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Various subtypes of IMP and PMP

1.a singgle pass glycosilated IMP:
transmembrane and make a single pass through the membrane

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Singlepass IMP,has 3 parts:

*a hydrophilic section,containing charged and
polar amino acids in the aqueous environment
outside the cell.
*a hydrophobic stretch of nonpolar amino acids
forming an alpha helix within the hydrophobic
core of the bilayer
*a hydrophilic portion within the aqueous
interior of the cell.
Referred to as a tripartite single pass
transmembrane protein
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Example:Glycophorin A,the major

sialoglycoprotein in the erythrocyte plasma
membrane
Glycophorin A: a membrane glycoprotein
containing 131 aa with its mass and all
carbohydrate on the external surface of the
membrane.

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The NH2 terminal segment is highly

hydrophilic,the hydrophobic segment,of 23
nonpolar aminoacids,makes a single pass
through the membrane as an alpha helix,and a
COOHterminal hydrophilic segment is
exposed at the cytoplasmic surface.
The function glycophorinA is unknown

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2. Multipass glycosylated IMP: makes

multiple alpha helical segment passes through the
membrane
found in transporters and membrane chanels.
Contain polar and even charged,amino acids within the
bilayer core.
These polar amino acids,when facing one side of the
alpha helix,constribute to the formation of aqueous pores.
Example: Band 3
Band 3:-is the erythrocyte anion exchange protein
- a homodimer or homotetramer,in which each
chain contains 929 amino acids.
- responsible for the one-for-one exchange of
HCO3- for Cl- across the erythrocyte membrane that
allows the release of CO2 in lungs.
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-Band 3 makes 12-14 alpha helical passes through the

membrane.
-it contains a small hydrophilic COOH-terminus and a
longer hydrophilic NH2-terminal domain extending into the
cytoplasm.
-the NH2 terminal domain has binding sites for glycolytic
enzymes,hemoglobin,and ankyrin .
-The CH moleties associated with band 3 are on the outside
surface of the erythrocyte membrane.
-most transmembrane proteins is glycoproteins,and the sugar
residues are almost always found on the non cytoplasmic
side of the membrane.
-all transmembrane protein are IMP,but not every IMP is a
trans membrane protein.
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3. IMP for which the protein itself does not enter the
bilayer.It is covalently linked to a fatty acid chain or by
sugars to PI(phosphatidyl inositol).
- IMP but Not transmembrane protein.
-IMP embedded in the hydrophobic core.
Peripheral MembraneProtein:PMP
-PMP can attach to the membrane surface by ionic
interactions with:- an IMP or another PMP or
-the polar head groups of the
phospholipids.
Example:spectrin.
-Spectrin is -PMP in erythrocyte
- a structural protein that is found on the
cytoplasmic surface of erythrocyte nembrane
-constitutes 20-25 % of the total MP

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Spectrin is attached to the membrane by an ionic

interaction with the PMP ankyrin which, in turn,
associates with the NH2 terminal hydrophilic
domain of band 3.
PROTEIN and LIPID DISTRIBUTION
CH portion of glycoprotein and glycolipid have an
asymetric distribution across biological membranes.
The sugar residues are almost always found on the
noncytoplasmatic side of the membrane.
so in the plasma membrane human cells,CH will
be outside the cell and for organelle membranes,CH
will be found within the lumen.
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Oligosaccharides are attached to

glycoproteins by:
-N- linkage to asparagine residues or
- O-linkage to serine or threonine.
-The CH moleties of glycolipids and glycoproteins
as well as glycosaminoglycans, which are
oligosacharides bound together by small protein
cores,make up a fuzzy coat observed on electron
microscopy of the outer surface of the plasma
membrane.fuzzy coat referred to as a
glycocalyxsugar chalice.
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-PROTEIN

also have an asymmetric

distribution.Spectrin is always associated with
the inner cytoplasmic leaflet of the erythrocyte
membrane.
Glycophorin A always has its terminal NH2
terminal domain out side the erythrocyte .and
its COOH terminal domain within the
cytoplasm.
Proteins can not flip-flop from one leaflet of
the bilayer to the other,so protein asymmetry is
absolute.
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Phospholipids are asymmetrically

distributed across the plasma membrane of
human cells.
The choline containing lipids :phosphatidyl
choline and spingomyelin are primarily in the
outer leaflet,where as the amine containing
phospholipids:phosphatidylserine and
phosphatidyl etanolamine,are in the inner
leaflet.
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Phospholipids within human cell plasma

membranes rarely flipflop from one leaflet
to the other.
PL are synthesized in the ER and their
assymmetry is established by specific
tranlocating enzymes within this membrane.

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CHOLESTEROL
a mayor component of biological
membranes.
The structure:amphipathic,with a polar
hydroxyl group,hydrophobic planar steroid
ring, and attached hydrocarbon.
interscalates between the phospholipids,
with its hydroxyl group near the polar head
groups and its steroid ring and hydrocarbone
tail parallel to the fatty acid chains of the
phospholipids and perpendicular to the
membrane surfaces.

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Cholesterol has a property different from PL in its

distribution.
Cholesterol is distributed on both sides of the
bilayer and can move across the bilayer in response to
shape changes within the plasma membrane ,because
the polar head group of cholesterol is a small hydroxyl
group cholesterol(unlike PL) can readily flip-flop
from one leaflet of the bilayer to the adjacent leaflet .

Cholesterol,tends to slow their lateral mobility.

The significance of the assymmetric distribution of
protein and PL across the plasma membrane is it
allows the 2 sides of the membrane to be functionally
distinct.
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.BIOLOGICAL MEMBRANE are FLUID,but

that does not mean that EVERY MEMBRANE

MACROMOLECULE is MOBILE

Membrane PL are capable of several type

of motion within biological membrane.
The PL can rotate very rapidly around a
central long axis.
The fatty acid chains of PL are flexible,with
greatest flexion toward the center of the
hydrophobic bilayer core.
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The flip flop of PL from one leaflet of the

plasma membrane to the other is rare event but
must occur to establish asymmetry after
synthesis in the ER.
PL can move laterally across a biological
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membrane at 37 c about 10 times per
second.Cholesterol,tends to slow their lateral
mobility.
IMP(Integral Membrane Protein)can also
rotate along their axis within the membrane,but
they do not flip-flop from one leaflet to the
other.
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When bivalent antibodies agains cell surface

antigens are added to a motil cell,the surface protein
tend to cross-link into large clusters called patches
and subsequenly,cap at trailing edge of the motile
cell.
This process,which requires energy ATP and is
blocked by chemicals that depolymerization of
actin ,
demonstrates that these surface antigens
are capable of lateral movement within the plane of
the plasma membrane
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Protein can be removed by detergens

To study the structure and function of
membrane proteins, first must isolate and
purify the protein.
Such proteins can be solubilized by detergents,
which have affinity for hydrophobic and for
water.
Detergents are amphipathic molecules that
disrupt membrane by intercalating into
phopholipids bilayer and solubilizing proteins
and lipids.
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Ionic detergent, such as: Sodium

dodecylsulfat (SDS) and sodium
deoxycholate, contain of charged
group.
-Nonionic such as: Triton X-100 lack a
charged group.
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In a mixture of oil and water the

detergent forms a monomolecular
film between two substances.
*Agitation of oil water mixture
breaks large
volume of oil into smaller droplets.
*At very low concentrations in pure
water
detergent are dissolve as isolated
molecules.
*As the concentration increases the

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*At high concentration nonionic detergents

higher than CMC(critical micelle concentration),
detergent solubilizes lipids,and integral
membrane proteins,forming mixed micelles
containg detergent,protein and lipid
molecules;
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*At concentration below the CMC,

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Summary
The basic structure of all biological membranes is the
closed phospholipid bilayer.
The lipid composition of the bilayer varies among the
diverse cellular membranes:
-glycolipids and cholesterol-plasma membrane.
-cardiolipin inner mitochondrial membrane
Membrane proteins can be classified into two broad
groups.An integral protein interacts directly with the
phospholipid bilayer and usually contains one or more
long helical sequences of hydrophobic amino acids.

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