1. PLASMA MEMBRANE
- The Gateway To The Cell
Shilpa S U
MSc. Biochemistry &
Molecular biology
2. Plasma membrane or cell membrane or cytoplasmic membrane is
the biological membrane that seperates the interior of all cells
from the outside environment.
Thin delicate structures.
Only 5 -10 nm wide
Provides framework in which components can be organized.
Selectively permeable to ions and organic molecules & controls
the movement of substances in and out of the cells.
Basic function- protect the cell from its surroundings
3. “Around 5000 plasma
membranes stacked one
on top of the other is
equal to the thickness
of a single page of a
book!!!!!!!!”
4. MEMBRANE FUNCTIONS–an overview
Compartmentalization
Scaffold for biochemical activities
Selectively permeable barrier
Transporting solutes
Responding to external signals
Attachment to the cytoskeleton & ECM
Intercellular interaction
Energy transduction
5. HISTORY
Models of membranes were developed long before membranes were
first seen with the electron microscopes in the 1950s.
In 1985 ERNST OVERTON (University of Zurich) hypothesized that
membranes are made of lipids because substance that dissolve in lipid
enters cells faster than those that are insoluble.
He placed plant root hairs into 100’s of different solutions containing
a diverse array of solutes
He discovered that the more lipid soluble solute rapidly enter the root
hair cells.
Attempts to build artificial membranes provided insight into the
structure of real membranes
In 1917 ,IRVING LANGMUIR discovered that phospholipids dissolved in
benzene would form a film on water when the benzene evaporated.
The hydrophilic heads were immersed in water
6. The first proposal that cell membranes contain a lipid
bilayer was made by two Dutch scientists E.GROTEL and
F. GRENDEL in 1925
They extracted the lipid from human RBC’s & measured
the amount of surface area the lipid would cover over the
surface of water
Surface area of water covered by extracted lipid = 2
Surface area of the RBC’s
Concluded that plasma membrane contained a
bimolecular layer of lipids ie,lipid bilayer.
7. PROPERTIES OF LIPID BILAYER
Lipid bilayer is a universal component of all cell membranes
It composed of two layers of fatty acids organized in two sheets.
The lipid bilayer is typically about 5 nm to 10 nm thick.
that contain both a hydrophilic and a hydrophobic moiety.
With the hydrophobic tails of each individual sheet interacting with
one another, a hydrophobic interior is formed and this acts as a
permeability barrier.
The hydrophilic head groups interact with the aqueous medium on
both sides of the bilayer. The two opposing sheets are also known as
leaflets.
The membrane is composed of lipids and proteins and sometimes even
carbohydrates
Impermeable barrier: passage of only selective molecules like water
and small hydrophilic molecules.
8. In 1935 H DAVSON and J DANIELLI proposed a sandwich model in which
the phospholipid bilayer was lined on both of its inner & outer surface
by a layer of globular proteins.
Early images from electron microscopes seemed to support the Davson
– Danielli model and until the 1960s it was considered the dominant
model.
In 1950,they revised their model and said that in addition to the outer
& inner protein layers , it was also penetrated by protein lined pores
for the polar solutes and ions to enter and exit the cell.
9. In 1972, S JONATHAN SINGER and GARTH NICOLSON of University of California
proposed ‘FLUID MOSAIC MODEL’ ,
Revised model that proposed that the membrane proteins are dispersed and
invidually inserted into the phospholipid bilayer.
In this fluid mosaic model, the hydrophilic regions of proteins and
phospholipids are in maximum contact with water and the hydrophobic
regions are in a nonaqueous environment.
10. STRUCTURAL ORGANIZATION
Bimolecular layer of amphipathic lipids (phospholipid bilayer)
2 segments with very different chemical properties
Polar heads (hydrophilic)face outside
5 to 10 nm thick
Contain phospholipids, proteins, and steroid molecules.
11. WHY “FLUID MOSAIC”???
A membrane is a mosaic
Proteins and other molecules are embedded in a
framework of phoshoplids.
A membrane is a fluid
Most proteins and phospholipid molecules can move
move laterally.
12.
13.
14. PHOSPHOLIPID BILAYER
Lipid bilayer is a universal component of all cell membranes.
The structure is called a "lipid bilayer" because it composed of two layers of
fatty acids organized in two sheets.
The lipid bilayer is typically about five nanometers to ten nanometers thick
and surrounds all cells providing the cell membrane structure.
With the hydrophobic tails of each individual sheet interacting with one
another, a hydrophobic interior is formed and this acts as a permeability
barrier.
The hydrophilic head groups interact with the aqueous medium on both sides
of the bilayer. The two opposing sheets are also known as leaflets.
15. The three main structures phospholipids form
in solution; the liposome (a closed bilayer),
the micelle and the bilayer.
16. Surfaces of a cellular membrane
Two surfaces of a cellular membrane
CYTOSOLIC FACE :faces the cytosol
EXOPLASMIC FACE: faces the exterior environment
In the case of cellular membranes
exoplasmic face is towards the interior and
cytosolic face towards the exterior of the organelle.
Exceptions are mitochondria , chloroplast, and
nucleus.
17.
18. Chemical composition of membrane
Proteins
• Integral
• Lipid
anchored
• peripheral
Polar lipids
• Phospholipids
• Glycerolipids
• Spingolipds
• Sterol
• cholesterol
Carbohydrates
• Glycolipids
• glycoproteins
19. Membranes are lipid protein assemblies ,held
together by non covalent bonds.
Lipid bilayer is the structural backbone of the
membrane.
It provides the barrier that prevents random
movements of water soluble materials in and out of
the cell.
The ratio of lipid to protein in a membrane varies
depending on the type of cellular membranes, type
of organism, & the type of cell.
20. MEMBRANE LIPIDS
The plasma membrane contains three principal classes of amphipathic
lipids (contain both hydrophobic and hydrophilic ends)
1. Phosphoglycerides; most abundant
2. Sphingolipids
3. Steroid: cholesterol
21. Phosphoglycerides
Most abundant lipid
They are built on a glycerol backbone ,so called as
‘phosphoglycerides’.
Membrane glycerides are diglycerides
Derivative of glycerol 3 phosphate
Contain a hydrophobic tail composed of 2 fatty acyl chains esterified
to the hydroxyl group in glycerol phosphate and a polar head
attached to phosphate group (fatty acyl chains can differ in no of
carbon they contain and degree of saturation)
Classified according to nature of head group
Without any additional substitutions beyond the phosphate and the
two fatty acyl chains – phosphatidic acid
23. Choline – forms phosphatidylcholine
Ethanolamine - phosphatidylethanolamine
Serine – phosphatidylserine
Inositol – phosphatidylinositol
Each of these groups are small & hydrophilic and together
with the –vely charged phosphate to which it is attached ,
forms a highly water soluble domain at one end of the
molecule called the head group
A membrane fatty acid may be fully saturated or
monounsaturated or diunsaturated.
Phoshphoglycerides often contains 1 saturated and 1
unsaturated fatty acyl chains.
Negatively charged phosphate group and hydroxyl group on
head groups interact strongly with water
24. Sphingolipids
Derived from amino alcohol sphingosine
Contains long hydrocarbon chain.
Long chain fatty acid attached by amide linkage to sphingosine amino
group - ceramide
Amphipathic
25. SPHINGOMYLEIN – most abundant sphingolipid ,in which phosphocholine is
attached to terminal –OH group of sphingosine
They are similar to the phosphoglycerides &can form mixed bilayers with
them
If carbohydrate is attached to sphingosine we get GLYCOLIPIDS
They consume 2 -10 % of total lipid in plasma membrane
If carb: is a simple sugar – cerebrosides
If cluster of sugars – gangliosides
They have crucial role in cell functions, nervous system is rich in glycolipids
Myelin sheath contains a high content of a glycolipid called galactocerebroside
which is formed when a galactose is added to ceramide
26. MEMBRANE STEROIDS
Consist of cholesterol and its analogues.
Abundant in mammalian cell, but absent in prokaryotes
and plant cells.
About 50-90% of cholesterol in mammalian cells is present
in plasma membrane and associated vesicles.
Oriented with their small hydrophilic -OH group towards
the membrane surface & remaining in the lipid bilayer.
Although almost entirely hydrocarbon, it is amphipathic
because its –OH group can interact with water.
Interfere with the movements of the fatty acid tails of the
phospholipids
27.
28. MEMBRANE PROTEINS
Associated with each membrane is a set of membrane proteins that enables
the membrane to carry out its distinctive activities .
The types of proteins attached to a membrane varies depending on cell type
and subcellular location.
Proteins associated with particular membrane are responsible for its distinctive
function.
Amount of protein also vary depending on subcellular location and cell type.
eg: inter mitochondrial membrane contain 76% protein, myelin membrane
contain 18% protein.
3 different types of protein: based on their intimacy of their relationship to the lipid
bilayer.
a) INTEGRAL MEMBRANE PROTEIN
b) LIPID ANCHORED MEMBRANE PROTEIN
c) PERIPHERAL MEMBRANE PROTEIN
30. INTEGRAL MEMBRANE PROTEINS
Trans membrane proteins( they pass entirely through the lipid bilayer)
Span a lipid bilayer and comprises 3 segments.
Cytosolic and exoplasmic face domains have hydrophillic exterior surface that interact
with aqueous solution on the cytosolic and exoplasmic faces of the membrane.
In contrast the membrane spanning segment contain more hydrophobic amino acids
whose side chains protrude outward and interact with the hydrophobic hydrocarbon
core.
Membrane spanning segment consist of 1 or more α helices or multiple β strands.
31. PERIPHERAL MEMBRANE PROTEINS
Do not directly contact the hydrophobic core of phospholipid bilayer.
Associated with the membrane by weak electrostatic bonds
Can be bound to either cytosolic or exoplasmic face of plasma membrane.
Cytoskeleton can be loosely associated with cytosolic face by one or more peripheral
proteins.
Such interactions provide support for various cellular membranes, helping to determine
cell shape and much properties, and 2 way communication between all exterior and
interior faces.
32. LIPID ANCHORED MEMBRANE PROTEINS
Also known as lipid-linked proteins
Located on the surface of the cell membrane that are covalently attached
to lipids by a small oligosaccharide linked to a molecule of phosphatidyl
inositol embedded within the cell membrane(GPI –anchored proteins).
Hydrophobic segment embedded in one segment of the membrane.
These lipids insert and assume a place in the bilayer structure of the
membrane alongside the similar fatty acid tails.
Polypeptide chain itself does not enter phospholipid bilayer.
The lipid-anchored protein can be located on either side of the cell
membrane.
Thus, the lipid serves to anchor the protein to the cell membrane.[1][2]
33. MEMBRANE CARBOHYDRATES
Depending on species & cell type carbohydrate conc:
varies from 2 – 10% by weight
More than 90% of membrane carbohydrate
covalently linked to proteins to form glycoproteins
and rest to form glycolipids.
Carbohydrates of the cell membranes face outside
into the extracellular space.
Carbohydrates of glycoproteins is present as short ,
branched hydrophilic oligosaccharides
Has an imp role in mediating proteins to different
cellular compartments
Carbohydrates of glycolipids of RBC plasma
membrane determine the blood type of a person.
34. MEMBRANE FLUIDITY
Physical state of a lipid membrane is determined by its fluidity.
Membrane fluidity is influenced by temperature, saturated or unsaturated,
fatty acid chain length, presence of cholesterol etc.
If the temperature of the bilayer is kept relatively warm,the lipid exists in a
fluid state.
As temperatures lowers, membranes switch from a fluid state to a solid state
as the phospholipids are more closely packed(frozen crystalline gel).
Saturated fatty acids have the shape of a straight flexible rod ,unsaturated
fatty acids have crooks/kinks in the chain at the site of a double bond.
35. Consequently phospholipids with saturated chains pack more tightly
than those containing unsaturated chains .
Shorter the fatty acyl chains of a phospholipids ,the lower its melting
temperature.
36. The steroid cholesterol is wedged between phospholipid
molecules in the plasma membrane of animal cells
At warm temperatures , it restrains the movement of
phospholipids and reduces fluidity
At cool temperatures it maintains fluidity by preventing
tight packing.
37. LATERAL MOBILITY OF LIPIDS
Thermal motion allows lipid molecules to rotate freely around long
axes and also to diffuse laterally within each leaflet.
Because movements are lateral, fatty acyl chains remain in
hydrophobic interior.
A typical lipid molecule exchange places with its neighbors in a leaflet
about 10^7 times/sec and diffuse several micrometers /sec at 37˚C.
These diffusions indicate that viscosity of plasma membrane is 100
times that of water- approx. that of olive oil.
A lipid molecule can diffuse the length of a bacteria in 1sec and that
of animal cell in 20secs.
Movement can be observed by Fluorescence Recovery after
Photobleaching (FRAP) technique.
38.
39. FLOURESCENCE RECOVERY AFTER PHOTOBLEACHING
Method for determining the kinetics of diffusion through tissue or cells.
It is capable of quantifying the two dimensional lateral diffusion of a
molecularly thin film containing fluorescently labeled probes, or to examine
single cells.
This technique is very useful in biological studies of cell membrane diffusion
and protein binding.
