1. STRUCTURE OF CELL MEMBRANE
&
CELLULAR JUNCTIONS
PRADEEP SINGH
M.Sc. MEDICAL BIOCHEMISTRY
HIMSR, JAMIA HAMDARD
2. CONTENTS
I. Introduction of Plasma Membrane
II. History
III. Fluid Mosaic Model
IV. Chemical composition of plasma membrane
V. Function of Plasma Membrane
VI. Cellular Junctions
3. INTRODUCTION
• Selectively permeable & helps in transport of substances with the help of
proteins such as integral and peripheral proteins.
• Involved in a variety of cellular process such as Cell adhesion, Ion conductivity
and Cell Signaling.
• Provide mechanical strength to the cell.
• Cell Membrane or Plasma membrane
separates the interior of cells from the
outside environment.
• Composed of a lipid bilayer, including
cholesterol which maintain their fluidity
under various temperature.
4. HISTORY
• The cell theory was proposed by Theodor Schwann and Matthias Jakob
Schleiden in the 1830s.
1. All living organisms are composed of one or more cells.
2. The cell is the most basic unit of life.
3. All cells arise only from pre-existing cells.
• The lipid bilayer hypothesis was proposed in 1925 by Gorter and Grendel.
• The most accepted biological model of cell membrane was given by SJ
Singer and G. L. Nicolson in 1972.
• First cell was discovered by Robert Hooke in
1665 using a microscope.
5. FLUID MOSAIC MODEL
• In 1972 SJ Singer and GL Nicolson proposed fluid mosaic model.
• Fluid – Individual phospholipids and some proteins can move
sideways (laterally) in each layer-therefore FLUID
• Mosaic – Range of different proteins resting on the surface on
through the phospholipid layer gives it a mosaic appearance.
7. • Cell membranes contain a variety
of biological molecules, mainly
lipids and proteins.
• Carbohydrates are present in very
small amount, predominately as
Glycoproteins.
• Composition is not set, but
constantly changing for fluidity and
changes in the environment.
CHEMICAL COMPOSITION OF PLASMA MEMBRANE
Plasma
Membrane
Lipids
40-45%
Proteins
50-55%
Carbohydrates
1-5%
8. • The cell membranes consists of
three class of amphipathic lipids:
phospholipids, glycolipids and
sterols.
• Carbohydrates are present in very
small amount, predominately as
Glycoproteins.
• Composition is not set, but
constantly changing for fluidity and
changes in the environment.
1. LIPIDS
Lipids
Phospholipids
> 55%
Glycoslipids
2%
Cholesterol
40-45%
9. • Phospholipids are the most abundant
lipids in the cell membranes.
• Phospholipids consists of two classes
based on the types of alcohol moiety:
Glycerophospholipids, Sphingolipids
• Plasma membrane is asymmetric I
nature i.e., contains different types of
phospholipids in the outer and inner
leaflet (result in increase in fluidity)
• Outer leaflet: Phosphatidylcholine and
Phosphatidylethanolamine
• Inner leaflet: Phosphatidylserine,
Phosphatidylinositol & Sphingomylein
Phospholipids Phospholipds
Glycerophospholipids
Phosphatidylcholine
Phosphatidylserine
Phosphatidylethanolamine
Phosphatidylinsositol
Sphingolipids
Sphingomylein
10. • Phospholipids are amphipathic molecules consist of a
polar head and unsaturated fatty acid tails.
• The unsaturation in the fatty acid chains prevents the
close packing of the plasma membrane.
11. • Glycolipids only accounts for 2% of the total lipids.
• The fatty acids in the glycolipids usually contain even number of carbon atoms, typically between 16 and
20.
Glycolipids
Cholesterol
• Cholesterol is normally found dispersed between the hydrophobic tails of the membrane phospholipids.
• Cholesterol regulates the fluidity of the plasma membrane.
• At high temperatures, cholesterol inhibits the movement of phospholipid fatty acid and reduced membrane
fluidity.
• At cold temperatures, cholesterol interferes with fatty acid chain interactions. Acting as antifreeze,
cholesterol maintains the fluidity of the membrane.
12. Fluidity Of Lipid Bilayer
Low temperature High temperature
Phase transition
• Fluid like organization.
• Polar head loosely packed
• Tails disordered.
• Membrane thinner.
• Gel like organization.
• Polar head tightly packed.
• Tails regular
• Membrane thicker
13. • Plasma membranes also contain carbohydrates,
predominantly glycoproteins.
• Carbohydrates are located on the surface of the
cell where they recognize host cells and share
information.
• Viruses and other parasites bind to these
receptors cause an infection.
2. Carbohydrates
14. • Plasma membrane has large content of proteins, typically around 50% of membrane volume.
3. Proteins
Type Description Examples
Integral proteins or
transmembrane proteins
Span the membrane and have a
hydrophilic cytosolic domain, which interacts with internal
molecules, a hydrophobic membrane-spanning domain
that anchors it within the cell membrane, and a hydrophilic
extracellular domain that interacts with external molecules.
The hydrophobic domain consists of one, multiple, or a
combination of α-helices and β sheet protein motifs.
Ion channels, proton
pumps, G protein-
coupled receptor
Lipid anchored proteins
Covalently bound to single or multiple lipid molecules;
hydrophobically insert into the cell membrane and anchor
the protein. The protein itself is not in contact with the
membrane.
G proteins
Peripheral proteins
Attached to integral membrane proteins, or associated with
peripheral regions of the lipid bilayer. These proteins tend
to have only temporary interactions with biological
membranes, and once reacted, the molecule dissociates to
carry on its work in the cytoplasm.
Some enzymes, some
hormones
15. Integral protein Peripheral protein
• Integral proteins are permanently
attached to the membrane.
• Embedded in the whole membrane.
• Serve as carrier proteins, channels,
&enzymes.
• Detergents should be used to
remove integral proteins.
• Glycophorin are the example of
integral proteins.
• Peripheral proteins are temporarily
attached to the membrane.
• Located on the inner or outer surface of
the phospholipid bilayer.
• Serve as receptors and surface antigens.
• Peripheral proteins removed by salt, pH
changes
• Erythrocyte spectrin are the example of
peripheral proteins.
16. • Ion channels allow inorganic ions such as sodium,
potassium, calcium, or chlorine to diffuse down their
electrochemical gradient across the lipid bilayer.
• Ion channels plays an important role in controlling the
electrical behavior of cells (i.e. nerve cells).
• A G-protein coupled receptor is a single polypeptide
chain that crosses the lipid bilayer seven times
responding to signal molecules (i.e. hormones and
neurotransmitters).
• G-protein coupled receptors are used in processes
such as cell to cell signaling, the regulation of the
production of cAMP, and the regulation of ion
channels.
17. Asymmetry Of Lipid Bilayer
Outer leaflets
• Lots of carbohydrates.
• Sphingomyelin and
phosphotidylcholine.
• Floppase is an outward-directed ATP-
dependent transporter.
Inner leaflets
• Carbohydrates does not have
significant role.
• Phosphotidylserine and
phosphotidylethanolamine.
• Flippase is an inward-directed ATP-
dependent lipid class of transporters.
18. FUNCTIONS OF PLASMA MEMBRANE
• Protective:- Forms outermost boundary of the cells.
• Digestive:-Takes in food and excretes waste products.
• Selective Permeability:-Helps in transport across the membrane.
• Contains cell surface receptors (e.g: Glycoprotein receptors present on RBCs).
• Cell Adhesion Molecules (Cadherins) present on the plasma membrane of certain
cells plays an important role in the process of inflammation.
• Junctions: Helps in formation of various types of junction (Adherens &
Anchoring) along with the help of cytoskeleton elements.
20. CELL JUNCTIONS
• The cell junction is a cell-cell or cell-
extracellular matrix contact within a
tissue of a multicellular organism,
especially abundant in epithelia.
• Combined with cell adhesion
molecules and extracellular matrix,
cell junctions help hold animal cells
together.
21. • Eukaryotic cells contain protein
filaments that are collectively called as
cytoskeleton.
• These cytoskeleton filaments plays an
important role in the establishment of
Cellular Junctions.
• These cytoskeleton elements also
helps in establishing cell shape,
provide mechanical shape, help in
locomotion of cell, chromosome
separation, intracellular transport of
organelles
22.
23. Cellular Junctions
There are two main ways in
which animal cells are
bound together.
1. Cell – Cell Junction
2. Cell – Matrix Junction
24. ANCHORING JUNCTIONS
• All four types of Anchoring junctions depends on cell adhesion molecules
(CAMs).
• These proteins span the plasma membrane with one end linking to the
cytoskeleton {cell-cell or cell – matrix}and other is exposed outside the
membrane.
• The primary function of Anchoring junction is to resist the external forces that
pull the cells apart.
• Cytoskeleton linked transmembrane protiens falls into four superfamilies.
1. Cadherins <cell-cell>
2. Integrins
3. Immunoglobulins
4. selectins
28. 1. Adherens Junction
• Cadherins (named for "calcium-dependent adhesion") are a
type of (CAM) that is important in the formation of adherens
junctions to bind cells with each other.
• Cadherins are a class of type-1 transmembrane proteins.
• Cadherins depends on calcium (Ca2+) ions for their function.
29. Classification of cadherins
• Classical cadherins
1) E-cadherin {Epithelial cells}
2) N- cadherin {Nerve cells and the lens cells}
3) P- cadherin {placental and epidermal cells}
• Non-classical cadherins
1) Protocadherins {found in brain}
2) Desmocollins and Desmogleins { Desmosomes}
31. 2. DESMOSOMES
• Desmos means ‘bound’ , Soma means ‘body’.
• It is also called Macula Adherens.
• Provide strong mechanical strength between the epithelial and
muscle cells.
• These junctions are small disk shaped ‘spot welds’ between
adjacent cells.
33. TIGHT JUNCTION
• Occupies the most apical
position
• Closely associated areas of two
cells.
• Form a seal b/w cells and a
fence between plasma
membrane domains.
• Selectively limits the diffusion
of water , ions, and larger
solutes as well as migration of
cells.
DIAGRAMATIC REPRESENTATION OF TIGHT JUNCTION
35. Gap junctions
• Gap junctions couple cells both electrically and
metabolically.
• It bridges gaps between adjacent cells to create direct
channels.
• Present in most animal tissues, including connective ,
epithelia and heart muscle.
• Half channels in each membrane called connexons.
• Connexons consists of six protein subunits, called
connexins.
( gases like O2,CO2,N2,lipids, steroid hormones, alcohol) can dissolve in the polar region of the membrane and move rapidly across the membrane.
( gases like O2, CO2, N2, lipids, steroid hormones, alcohol) can dissolve in the polar region of the membrane and move rapidly across the membrane.
Attachment to cell and matrix control the orientation and behaviour of cells cytoskeleton , therby allowing cells to sense and respond to changes in the mechanical features of their environment. Thus the apparatus of cell junctions and extracellular matrix are critical for every aspects of organisation ,fxn and dynamics of multicellular structures.
There is specialization within each family : some cadherins link to actin and form adherens junction and some linked to intermediate and form desmosomes.
But there are some exceptions to these rules in case of integrins. Eg. Some mediate cell-cell rather than matrix.
The large no. of non classical cadherins more than 50 found in brain alone.
Together both cadherins constitute about 180 members in humans.
The cadherins are coupled indirectly to actin filaments through an adaptor protein complex containing p120-catenin, β-catenin, and α-catenin. Other proteins, including vinculin, associate with α-catenin and help provide the linkage to actin. β-Catenin has a second, and very important, function in intracellular signaling
These cells are specialized for absorption of nutrients; at their apex, facing the lumen of the gut, they have many microvilli (protrusions that increase the absorptive surface area).