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Medical Cell Biology

Chapter 3

Cheng Xiaoli Zhengzhou University


Medical Cell Biology

Content
3.1.sMembrane components and
structure of biomembranes
3.1.1. Membrane Lipid
3.1.2 Steroids
3.1.3. Membrane Protein
3.1.4. Membrane carbohydrate
3.1.5. Membrane Fluidity
3.1.6. Membrane asymmetry
3.1.6. Modals of cell
3.1.6. Common function of
Membrane
Membrane Cheng Xiaoli Zhengzhou University
Medical Cell Biology

Membrane Basic Concepts


All Cell surrounded by a layer of membrane
contained special kind of lipids, proteins and
sugars, called cell membrane.
Some Cell such as plant cells
and some bacteria cells,
contain a cell wall in
appearance of the plasma
membrane, or contain a capsule
surrounding the cell wall, or
contain some special
structures on the surface of
plasma membrane, such as cell
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Medical Cell Biology

Membrane Basic Concepts


A living cell is a self-reproducing system of
molecules hold inside a container. The
container is the plasma membrane, which
forms a dynamic interface between the
cytosol and the environment.
plasma
membrane

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Medical Cell Biology

Membrane Basic Concepts


In eukaryote cell, some membrane
compartmentalize the cell into smaller
subcompartments termed organelles, such as
endoplasmic reticulum , vesicle , Golgi body ,
mitochondria , etc. each organelle surrounded by
one or more
All this layer of
membrane membrane.
form
closed structures
surrounded b y one or
more layer of membrane
System. The plasma
membrane and
cytoplasmic membrane
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Medical Cell Biology

3.1 Components and


structure of
biomembranes
Basic compositions of all membrane are lipids,
proteins and a small quantity of saccharide.
3.1.1
Lipid
The cellular plasma and organelle membranes within
your body contain 40% to 80% lipid. Among these
lipids, the phospholipid are the most prevalent.
Lipid contended in a typical biomembrane are
phospholipids ( phosphoglycerides ) and steroids. All
three classes of lipids are amphopathic molecules.
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Medical Cell Biology

Main Kinds of Membrane


Lipid
•Phosphatidylethanolamine(PE) 磷脂酰乙
醇胺
•Phosphatidylserine (PS) 磷脂纤丝氨

•Phosphatidylcholine (PC) 卵磷脂


•Sphingomyelin (SM) 神经 ) 鞘磷

•Cholesterol (CH) 胆固

•Glycolipid (GL) 糖磷脂

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Medical Cell Biology

Lipid composition of some


biomembranes
Membrane PE PS PC SM GL CH Other
RBC plasma membrane 18 7 21 18 3 26 13
Liver plasma membrane 7 4 24 19 7 17 22
Mitochondrial membrane 35 2 39 0 trace 3 21
Endoplasmic reticulum 17 3 40 5 trace 6 27

PE: phosphatidylethanolamine 磷脂酰乙醇胺 GL: glycolipid


PS: phosphatidylserine 磷脂纤丝氨酸 PC: phosphatidylcholine
卵磷脂

SM: sphingomyelin 鞘磷脂 CH: cholesterol


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Lipids
Medical Cell Biology

Structure HO phosphate
A typical O=P
O-
phospholipid hydrophilic O
head CH 2 CH CH 2
molecules consists O O glycerol
of a amphipathic C=OC=O

lipids, part water-


soluble and part
hydrophobic
water-insoluble tail
since they have both Fatty acid
tail
hydrophilic ( or
water-loving) polar Phosphatidic acid is the most
head groups and simplistic PL. It is a promolecular
to be linked with other molecular
hydrophobic ( or to form different PL
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Saturated and CH2 N+ (CH3) 3


CH2
Unsaturated Fatty O
O P =O
Acid Tail O
CH2 CH CH2
•The fatty acid tail on O O
the left is saturated , C=O C=O
CH2 CH2
meaning that every CH2 CH2
carbon atom is linked CH2 CH2
to two or three CH2 CH2
CH2 CH2
hydrogen atoms.
•The tail on the right is CH2
CH2
CH2

=
CH
unsaturated , with a CH2 CH2 animated
double bond between model
…..


.

..
carbon atoms at the CH2
.
CH3
point indicated by the CH3

arrow. Cheng Xiaoli Zhengzhou University


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Saturated and
Unsaturated Fatty
Acid Tail

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Bilayer structures
• All kinds of phospholipid molecules in
biomembrane contain a core or called “nonpolar
tail” and a hydrophilic core or called “polar head”.
This molecular character makes phospholipid
have ability, in certain conditions, to form a
spherical bilayer structures called liposome.
• In fact, this is also the basic
pattern of phospholipid in the
natural biomembrane. The
bilayer structures make up of
basic framework of
biomembrane.
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Medical Cell Biology

Effects of Variation in
Phospholipid Fatty Acid
Composition
(a) If a lipid layer is composed entirely of
saturated fatty acids, the fatty acid tails
nest together to form rigid structures.
(b) In unsaturated fatty acids, a double
bond causes a deformation that interferes
with the orderly stacking of the molecules
and makes the fatty acid region more fluid.
(c) When more double bonds are present,
the deformations and resulting fluidity are
greater still.
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Effects of Variation in
Phospholipid Fatty Acid
Composition

Tight-knit Form Full of Free Space Form

• On the nature of the hydrocarbon tails: the closer and


more regular the packing of the tails, the more viscous
and less fluid the bilayer will be.

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G lycolipid
Glycolipids: like phospholipids, these
compounds are composed of a hydrophobic
region, containing two hydrocarbon tails, and
a polar region, which, however, contains one
or more sugar residues and no phosphate.

Sugar residues Polar head


chain

nonpolar tail

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Glycolip
id
Glycolipid are more minor components of human and
other animal membranes. Sugar residues of plasma
membrane glycolipids almost always face the outside of
the cell; that is, they have an asymmetric distribution,
being found only in the outer leaflet of the bilayer.

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3.1.2
Medical Cell Biology

Steroids
• Steroids include cholesterol and certain hormones.
Cholesterol is a common component of animal cell
membranes.

• Cholesterol molecules intersperse among phospholipid


tails in the bilayer or filled spaces between neighboring
phospholipid molecules that are caused by the kinks in
phospholipid molecules unsaturated hydrocarbon tails. In
this way cholesterol stiffens the bilayer and makes it less
fluid and less permeable. Cheng Xiaoli Zhengzhou University
3.1.2
Medical Cell Biology

Steroids
Cholesterols is amphiphathic because its hydroxyl
group can interact with water. And Cholesterols is a
saturated molecule, without double bond between
carbon atoms . HO
polar head CH3

CH3

CH
rigid planar CH3 CH
steroid ring 2
structure CH2
CH2
H3C CH
Nonpolar animated model
CH3
(hydrocarbon)
hydrocarbon
tail cholesterolCheng
formula
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Medical Cell Biology

• Cholesterol has a number of functions


• It is a structural component of cell membranes.
The ratio of cholesterol to polar lipids affects the
stability, permeability, and protein mobility of a
membrane. Membranes with high ratios have high
stability and relatively low permeability; their major
function is a protective barrier.
• Cholesterol is stored in the adrenals, testes, and
ovaries, chiefly as the fatty acid ester, and converted to
steroid hormones.
• In the liver cholesterol is the precursor of the bile acids.
• Low levels cholesterol might cause less flexibility of our
blood vessel, low power to resist disease and…
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Medical Cell Biology

3.1.3 Membrane Protein


The hydrophobic core is an impermeable
barrier that prevents the diffusion of
water-soluble solutes across the
membrane. This simple barrier function
is modulated by the presence of
membrane proteins that mediate the
transport of specific molecules, ions, and
water across this otherwise impermeable
bilayer.

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Medical Cell Biology

3.1.3 Membrane Protein


The protein associated with a particular
membrane are responsible for its distinctive
activities. The complements and density of
proteins associated with biomembranes vary
acutely depending on cell type and
subcellular location. The importance of
membrane proteins is suggested from the
finding that approximately 1/3 of all yeast
genes encode membrane proteins. The
relative abundance of genes for membrane
proteins if even greater in multicellular
organisms. Cheng Xiaoli Zhengzhou University
Medical Cell Biology

Three forms proteins link to membrane :


integral proteins (transmembrane
proteins) , lipid-anchored membrane
proteins and peripheral membrane
proteins.
transmembrane
Glycosylated integral protein
integral protein

peripheral membrane protein Lopid-anchored


with covalent lipid linker membrane protein with
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Integral proteins or
Medical Cell Biology

transmembrane
proteins)
Some integral membrane proteins are
transmembrane and make a single or multiple
α-helical passes through the membrane.
Integral protein can be marked off three
different segment called domains:
exoplasmic domain

transmembrane domain

Cytosolic domain

Cheng Xiaoli Zhengzhou University


Integral proteins or
Medical Cell Biology

transmembrane
proteins)
• The cytosolic and exoplasmic domain have hydrophilic
exterior surfaces that interact with the aqueous solutions
on the two faces of the membrane.
• The membrane-spanning domain ( transmembrane
domain ) form channels and pores, that allow move
molecules in and out of cells
exoplasmic domain

transmembrane domain

Cytosolic domain

Cheng Xiaoli Zhengzhou University


Integral proteins or
Medical Cell Biology

transmembrane
proteins)

•Glycophorin A always
has its NH2 -terminal
domain outside the red
cell and its COOH-
terminal domain within
the cytoplasm.

Cheng Xiaoli Zhengzhou University


Integral proteins or
Medical Cell Biology

transmembrane
proteins)
• The exoplasmic domain on the extracellular
surface of the plasma membrane generally
bind to other molecules, including external
signaling proteins, ions, and small
metabolites, and to adhesion molecules on
other cells or in the external environment.

Cheng Xiaoli Zhengzhou University


Integral proteins or
Medical Cell Biology

transmembrane
proteins)
• The transmembrane domain lying along the
cytosolic face of the plasma membrane have a
wide range of functions, from anchoring
cytoskeletal proteins to the membrane to
triggering intracellular signaling pathways.

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Medical Cell Biology

Lipid-anchored membrane
proteins
-NH2

outside

lipid
bilayer

inside
-COOH
• Lipid-anchored membrane proteins are
bound covalently linked to one or more
lipid molecules. The polypeptide chain
itself does not enter the bilayer.
Cheng Xiaoli Zhengzhou University
Medical Cell Biology

Peripheral membrane
protein
• Peripheral protein do not interact with the
hydrophobic core of the phospholipid bilayer.
They just attach to the membrane surface by
ionic interaction with an integral membrane
protein or another peripheral membrane
protein, or by interaction with the polar head
groups of the phospholipids.
• Peripheral
protein are
localized to
either the
cytosolic or the
exoplasmic face
of the plasma Cheng Xiaoli Zhengzhou University
Medical Cell Biology

There are various subtypes of


integral and peripheral membrane
proteins.

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Medical Cell Biology

3.1.4 Membrane carbohydrate


• The content of membrane carbohydrate in is 2-10 percent
in membrane, and varies depend on the difference of cells.
for example, there are proteins 52%, lipids 40% and
carbohydrate 8% in the membrane of red cell.
• Some carbohydrate combine with membrane lipid and
form glucolipids via covalent bond, about 7% in red cell.
The others combine with membrane proteins and form
glucoproteins via covalent bond, about 93% in red cell.

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Medical Cell Biology

3.1.4 Membrane carbohydrate


• It is important that all membrane carbohydrate
pitch on the outside of plasmamembrane, but on
the inside of the endomembrane system.

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Medical Cell Biology

3.1.4 Membrane carbohydrate


• The function of membrane
carbohydrate
1) Improve the stability of membranes.
2) Advance the fastness of to proteinase in
extracellular matrix.
3) Help membrane proteins to form and
maintain the correct packing and three-
dimensional configure.
4) Take part in the processes of cell signal
recognition, cell adhension and cell junction
5) Give a correct position for transfer and
orientation of new protein.
6) Lectin a class of glucoproteins, protect the
cell and seed.
7) Some glucolipids are important blood group
determinants.
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Medical Cell Biology

3.1.5 membranes
fluidity
• Biological membranes are fluid,
but that does not mean that every
membrane macromolecule is
mobile.
• Phospholipids determine the
fluidity of the membrane and are
influenced by temperature,
saturation of fatty acid chains and
cholesterol.
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Medical Cell Biology

3.1.5 membranes
fluidity Flip-flop
(rarely occurs) Rotation

Lateral diffusion
(frequent)
• Phospholipids are able to move laterally across the
membrane at very fast rates.
• They are capable of transbilayer movement (flip-flop)
in the endoplasmic reticulum, but flip-flop is a rare
event in the plasma membrane.
• They can rotate rapidly around a central axis.
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3.1.5 membranes
fluidity
Integral membrane proteins can also
rotate along their long axis within the
membrane, but they do not flip-flop from
one leaflet to the other.
Several lines of evidence have indicated
that membrane proteins are also capable
of lateral movement within the plane of
the membrane.
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Medical Cell Biology

membrane 0 minute
protein

mouse cell human cell

cell fusion After 40


minute

Hybrid cell

Specific Fluorescent
antibodies Become mixed together

The use of cell fusion to reveal mobility


of membrane proteinsCheng Xiaoli Zhengzhou University
Medical Cell Biology

3.1.5 membranes
fluidity 100

50

0
5 15 25 35

• The fluidity of membrane proteins is affected


by temperature.
The percentage of mosaic cells increases sharply
as the temperature rises above 15℃, suggesting
that the lipid undergoes a phase transition in that
range from a gelating state to a fluid state
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Medical Cell Biology

Membrane phospholipids determine


membrane transition temperature and how
fluid membrane is at a certain
temperature.
•The closer and more regular the packing of
the hydrocarbon tails of the phospholipids,
the more viscous and less fluid the
membrane is.
•The larger proportion of unsaturated
hydrocarbon tails the membrane contains,
the more fluid the membrane is (because
each double bond in an unsaturated tail
creates a small kink in the tail, which makes
it more difficult for the tail to pack against
one another) .
•The more longer the fatty acid chain length of the tail, the
more likely the hydrocarbon tails interact with one
another, therefore decreasing the fluidityCheng
of the
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
• It is important when thinking about membranes
to keep in mind that a typical cell membrane
tends to have a different composition on one side
(inner leaflet ) than on the other (outer leaflet ).
•Cell membranes are generally asymmetrical,
presenting a very different face to the interior of
the cell or organelle than to the exterior. The two
halves of the bilayer often includes strikingly
different selections of phospholipids and
glycolipids. Moreover, the proteins are embedded
in the bilayer with a specific orientation, which is
crucial for their function.
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids
asymmetry
Lipids in biological membranes are
asymmetrically distributed across the bilayer; the
amine-containing phospholipids are enriched on
the cytoplasmic surface of the plasma membrane,
while the choline-containing and sphingolipids
are enriched on the outer surface.
The maintenance of transbilayer lipid asymmetry
is essential for normal membrane function, and
disruption of this asymmetry is associated with
cell activation or pathologic conditions.
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids
asymmetry
TPL
50 exoplasmic
SM PC
25 PE
PS
20%
10%

25 90%
80% cytosolic
50
The asymmetric distribution of phospholipids in
the plasma membrane of human RBC
PE: phosphatidylethanolamine 磷脂酰乙醇胺 GL: glycolipid
PS: phosphatidylserine 磷脂纤丝氨酸 PC:
phosphatidylcholine 卵磷脂 SM: sphingomyelin 鞘磷脂
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids
asymmetry

PS is negatively charged of phospholipid kinds, that is


why inner monolayer is negatively charged whereas
external monolayer is positively charged. Therefore, the
lipid bilayer can be considered as composed of two
relatively stable, independent monolayers with different
physical and chemical properties .
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids New
asymmetry phospholipid
molecules
•The lipid
asymmetry begins
at the point of
manufacture. New Phospholipid
synthesis
phospholipid Lipid bilayer of ER adds to
cytosolic half
Flippase
catalyzes
molecules are of the bilayer transfer of
synthesized by ER- phospholipid
molecules
membrane-bound
enzymes that
fatty acids use
available in the cytosolic
monolayer and release the newly Symmetric growth of
made phospholipid into the same both halves of bilayer
monolayer.
To enable the membrane as a whole to grow, a
proportion of the lipid molecules then have to
be transferred to the opposite monolayer.
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids
asymmetry

This transfer is catalyzed by enzymes called flippase. It


has been suggested that the flippases may transfer
specific phospholipid molecules selectively, so that
different types become concentrated in the two halves of
the monolayer.
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.1 lipids
asymmetry

Loss of Membrane Asymmetry


Loss of membrane asymmetry (phosphatidylserine redistribution)
is a very early event in Apoptosis. Anti-Phosphatidylserine is used
to detect the flip.
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.2 portions
asymmetry
1. many different kinds of
proteins are in the cell
membranes
a. each type has a unique
conformation and orientation
b. flip flop of proteins does not
occur, so their asymmetry is
absolute
c. conformational changes of protein can occur
2. carbohydrates of glycoproteins always at outer
surface
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3.1.6. Membrane
Medical Cell Biology

asymmetrically
3.1.6.3 sugar residues
asymmetry
•The sugar residues are always found on the non-
cytoplasmic side of the membrane.

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Medical Cell Biology

3.1.7 Modals of cell


Membrane
It is upon the works of
Danielli and Davson’s
"sandwich type" Membrane
modal, Robertson’s Unit
Membrane Model, and the
others scientific
achievements that Singer
and Nicholson proposed the
fluid mosaic model of
membranes In 1972, stating
that the membrane proteins
are globular and to float
within the lipid bilayer.
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3.1.7 Modals of cell
Medical Cell Biology

Membrane
• The Fluid Mosaic Model
The globular membrane proteins are embedded
within the bilayer, with hydrophobic portions of the
proteins buried within the hydrophobic core of the
lipid bilayer, and hydrophilic portions of the
proteins exposed to
the aqueous
environment, and
the proteins float
within the lipid
bilayer.

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3.2 Modals of cell
Medical Cell Biology

Membrane
The fluid mosaic model was modified many
times later because of more recent
discoveries, but it still remains the model
preferred by biologists today. It explains the
current knowledge of membrane structure and
also serves as the basis for our understanding
of how membranes function.

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Medical Cell Biology

3.2 Common functions of plasma


membrane
1. Plasma membranes act as a permeability
barrier that prevents the entry of unwanted
materials from the extracellular milieu and the
exit of needed metabolites.
2. In animal cells specialized areas of the
plasma contain proteins and glycolipids that
form specific junctions between cells to
strengthen tissues and to allow the exchange of
metabolites
3. Certain plasma membrane proteins anchor
cells to components of the extracellular matrix.
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Medical Cell Biology

3.2 Common functions of plasma


membrane
4. Certain plasma membrane contain receptor
proteins that bind specific signaling
molecules(e.g., hormones, growth factors,
neurotransmitters), leading to various cellular
responses.
5. Plasma membrane take part in the compart-
mentalization of cell.
... and many others functions of the plasma
membrane in bacterial, fungal, and plant etc.

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Medical Cell Biology

Summar
y
1. The plasma membrane is a selectively
permeable barrier found on the surface of
2. The basic structure of biological membranes
cells.
is a lipid bilayer.
3. There are three basic types of membrane
proteins: integral proteins (transmembrane
proteins) , lipid-anchored membrane proteins
and peripheral membrane proteins.
4. Proteins, sugar residues and lipids are
asymmetrically distributed across membranes.
5. Biological membranes are fluid.
Cheng Xiaoli Zhengzhou University
Medical Cell Biology

QUESTION
S Variation in Phospholipid
1. What is the Effects of
Fatty Acid Composition ?
2. What are the functions of membrane carbo-
hydrate ?
3. Please explain the statement: plasma mem-
brane is asymmetrical membrane.
4. What is the Fluid Mosaic Model ?
5. What factors affect the degree of membrane
fluidity ?
6. What are Common functions of plasma
membrane in cells ?
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