CELL MEMBRANES

 The Cell membrane

o The external boundary of cytoplasm or vacuole.
o It defines the cell and determines the nature of interaction of the cell.
o Controls the substances that enter and exit the cell [allows only certain
substances].
o Helps in adhesion of cells with each other and with the extracellular matrix
o Major contribution to cell identification that helps in tissue formation.
o The receptors of the cell membrane act as attachment sites for hormones
and growth factors.
o The receptors also help in activation of intracellular responses.
o The mutations in gene encoding receptors tend to cause malfunction in
signal transmission and allowance of foreign disastrous particles [ viruses]

Components of the cell membrane and its functions

o Lipids- There are two types of lipids that play an important role in
the function of cell membrane. They are:-
1. Phospholipids
- Structure- it consists of a 3C glycerol backbone with 2 fatty acids
attached to 1C and 2C and a phosphate group attached to 3C.
- They contain a hydrophilic head [water loving] and a hydrophobic
tail [water hating]. Therefore called an amphiphillic molecule
- The head carries a neg
negative
ative charge whereas the tail has no charge.
- When placed in water they tend to form clusters[ micelles]
micelles
2. Cholesterol
- They are lipids but have completely different structures.
- They are structures that have four fused carbon rings.
- They are usually present in between two phospholipids
- Their main function is to maintain membrane fluidity.
 Important cell membrane lipids
- Phosphotidylcholine [PC]
- Phosphotidylethanolamine [PE]
- Sphingomyelin [SM]
- Phosphoidylserine [PS]
- Phosphotidic acid [PA]
- Phospsotidylinositols
itols [PI]

 Lipid structure and membran

membrane curvature:
- In The curved portion of the membrane, the outer leaflet contains
lipids that are cylindrical whereas the inner leaflet contains lipids
that are conical shaped.
- This creates an asymmetrical distribution o off lipids in the two
layers, with PC largely in the oute
outer [cylindrical] and the PE in
largely in the inner leaflet [conical].[[ PE helps in membrane
curvature]
- Using the RBC cells for further studies, we observe that SM is
enriched in the outer leaflet whereas PI and PS are enriched in the
inner leaflet.
- This asymmetric distribution of lipids is responsible for the
biconcave shape of the RBC, and any change in its shape affects
its function.
- In aged RBC cells the asymmetry is broken; The PS becomes more
in the outer. This creates a signal that alerts the macrophage to
clear the aged RBC.
- In the RBC membrane, the choline containing phospholipids are PC
and SM and are enriched on the extracellular leaflet of the
phospholipid bilayer.

 Bilayer asymmetry :
- In the above example the PS has moved from the inner to outer
leaflet, this movement is unfavorable as the hydrophilic head
might have to cross the hydrophobic core of the bilayer
- The lipids move by active transport driven by proteins
- Types of proteins –
- 1. Flippase – move molecules against the concentration gradient
from outer leaflet to inner leaflet [ maintains membrane fluidity }
- 2. floppase-moves lipids against the concentration gradient from
inner to outer leaflet [maintains membrane fluidity]
- 3. scramblase- moves lipids in both directions but along the
concentration gradient [ destroys membrane fluidity ]
- The compositions of lipids differ from region to region. E.g.
SM – least in E.R membrane, less in the Golgi membrane, and
highest in the cell membrane.
 The lipid raft contains more SM,
The outer leaflet has more PC as well as SM than the inner leaflet.
Cholesterol is abundant in cell membrane than in E.R membrane
and Golgi membrane
- This is because the mode and site of synthesis varies. The lipids
are synthesized in the E.R and in Golgi.

Membrane fluidity
- The lipid composition plays major role in maintaining the cell
membrane’s fluidity.
- In saturated [single bonds] forms of Phospholipids, the Fatty acid
[FA] tails are bound to Hydrogen atoms and the absence of
double bonds makes the tails straight.
- In unsaturated [ double bonds] phospholipids the FA tails do not
have hydrogen bonds and double bonds are present which makes
the hydrocarbon tails to bend [approx 30 degree]
- When temperature decreases, the saturated fatty acids become
rigid, whereas the unsaturated fatty acids still maintain the space
that is created by the elbow of the bent chain. . This helps in
maintenance of the membrane fluidity and protects the cell from
rupturing.
- Organisms like fishes are capable of adapting to colder
environments by regulating their proportion of unsaturated fatty
acids.
- Cholesterol molecules control the effect of temperature on
membrane fluidity; they prevent the situations of low
temperature [rigidity] as well as high temperature [excess
fluidity].
- Cholesterol molecules are capable of inserting itself into the fatty
acid tails of the phospholipid; it therefore interferes with the
saturated tails and disturbs the tight packaging.
- The lipid raft rigidity is caused by tight packaging of cholesterol
molecules.
- The loosely attached integral proteins and lipids bring a fairly
good rigidity.

o Proteins
- Second major component of the cell membrane. They can be
present as
1. Integral proteins:
- They integrate completely into the membrane and embedded
within the phospholipid layer
- They have a hydrophobic transmembrane segment that is
capable of interacting with the hydrophobic region of
phospholipid bilayer.
- They sometimes associate with a single membrane or stretch
along both sides of the membrane.
- Up to 12 single protein segments comprise some complex
proteins, which are extensively folded and embedded in the
membrane
- Lipid-anchored protein [a type of integral protein] has a lipid
molecule that is covalently attached to an amino acid side chain
within the protein. The fatty acyl tails are inserted into the
hydrophobic portion of the membrane and thereby keep the
protein firmly attached to the membrane.
2. Peripheral proteins:
 - They are seen on both surfaces.
-They are non-covalently
covalently bound to the hydrophilic regions
-Sometimes
Sometimes they are attached to the integral proteins or
phospholipids.
-The
The peripheral proteins attached with the integral proteins help
in enzyme activity, attachment of cytoskeleton’s fibers, cell
recognition [called specific proteins, that attacks the foreign
proteins associated with invasive pathogens]

o Carbohydrates
- They are chains that contain 2 to 60 monosaccharide units.
 - They are always on the cell’s exterior
- They are usually found attached to proteins [glycoprotein] or
lipids [glycolipid].
- Blood type of a person refers to the type of glycolipid a person
has.
- They stabilize membrane structure by forming bonds with water.
- They act along with the integral proteins and help in cell
recognition [ allows immune system to differentiate between self
and non self cells]
- They form the glycocalyx [ used in cell to cell attachment leading
to formation of tissues]
- They are used as receptor molecules binding with the hormone or
neurotransmitter molecules triggering cell chemical reactions.

The protein, lipid and carbohydrate proportions in the plasma

membrane vary with cell type:

- Human cell 50% protein, 40% lipid, 10% carbohydrates

- Myelin which is an outgrowth of cell membrane in nerve cells
contain 18% protein and 76%lipid
- Mitochondrion inner membrane has 76% protein and 24% lipids
- RBC has 30% lipids
- The protein: lipid ratio in a typical cellular membrane is 1:1 and that
of the inner mitochondrial membrane is greater than 1:1
  How viruses infect cells?
- Glycolipid and glycoprotein on the cell membrane pave way for
some viruses.
- Examples: HIV and Hepatitis viruses that attack liver cells
- These viruses invade the cell as cells have binding sites on their
surfaces.
- The antigen [pathogen’s protein] contains the recognition sites for
the binding of immune cells to produce antibodies.
In case of HIV these recognition sites change rapidly sue to
mutations making it difficult for the body’s immune system to
recognize them and destroy them

 Disruption of membrane asymmetry:

- Scott syndrome: a rare congenital bleeding disorder caused by
disturbances In regulating membrane phospholipid asymmetry
- Apoptotic cells: the membrane asymmetry is disturbed in cells
that have reached the end of its life cycle. This process is called as
programmed cell death where the PS moving to the outer
membrane gives an ‘eat me’ signal for their removal

Fluid mosaic model

- This model explains the structure of the cell membrane
- According this model the cell membrane is made up of two
phospholipid layers, with each layer having the hydrophilic head
facing outwards and the hydrophobic tails facing inwards, facing
each other. [sandwich]
- This phospholipid bilayer also contained proteins, cholesterol
molecules and carbohydrates.
- Half of a phospholipid bilayer is termed a leaflet.
- This membrane maintains a stable fluidity
- Its ranges from 5 to 10 nanometer in thickness
- The individual molecules remain in close association yet have the
ability to readily move within the membrane. Though membranes
are often described as fluid, it is more appropriate to say they are
semi fluid.
- The cell membranes outer surface is hydrophilic and the cell
membrane’s interior is hydrophobic.
- This makes the head in contact with the fluid in and out of the cell
as it is hydrophilic and the tails being hydrophobic tend to repel
from water molecules.

 Membrane permeability
- The cell membrane is highly permeable to small uncharged
molecules like CO2, N2, O2 and Ethanol
- It is moderately permeable to molecules like water and urea
- It has low permeability towards polar organic molecules and
sugars
- This selective permeability is due to the phospholipid bilyer and
the presence of transport proteins

Membrane transport
Two types:
1. Passive transport
- This type of transport takes place along the concentration
gradient [from high conc. Region to low conc. Region]. They have
the following types:
 Diffusion
- Through the semi permeable membrane it moves substances
from area of higher conc. to lower conc. Down the gradient
- Examples: gas exchange during respiration and gas exchange
during photosynthesis
 Osmosis
- Movement of water molecules through a semi permeable
membrane down the gradient
- When the solute cannot pass through the semi permeable
membrane the water moves through the membrane and balances
the solute concentration.
- Isotonic – solute conc. Is same extra and intra cellularly
Hypertonic- solute conc. outside the cell is greater and water
content is less outside
Hypotonic- solute conc. outside the cell is less and water content
is more outside
- In the hypertonic and hypotonic situation the water moves from
higher conc. To lower conc. And balances. E.g. RBC cells in
hypertonic conditions shrink and in hypotonic situation swell up.
- In case of plant cells , they cannot shrink due to the presence of
cell wall instead they become placid [ plasma membrane shrinks and
cell wall moves away from it causing plasmolysis]. The cell wall
prevents the expansion or swelling of the cell when placed in
hypotonic in this situation the vacuoles help in swelling or
shrinking.
- The loss of turgor pressure leads to wilting In plants which is
vacuole filled with water
 Wilting

 Facilitated diffusion:
- The movement of certain materials across the plasma membrane
with the help of membrane proteins
- It happens along with the existing concentration gradient without
expending cellular energy.
- The facilitated transport proteins are integral proteins that help in
the movement of molecules through the hydrophobic parts of the
membrane. These proteins are of two types:
 Channels
- They contain hydrophobic domains as well as hydrophilic domains
that extend throughout the length of membrane having cytosolic,
extracellular and transmembrane domains.
- They help in extremely rapid movement of solutes [ up to 200
million ions/ sec ]
- Example aquaporins channels that helps in movement of water.
Osmosis is greater in cells that have the membrane channels
- Most of them are gated [controlled opening and closing] example:
ligand gated channels- controlled by non-covalently bound small
molecules like hormones or neurotransmitters.
- When open solute diffuses through the channel to reach the
other side
- When closed even in the presence of conc. Gradient no diffusion
is taking place.

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 Carriers
- They bind to the substance and thus trigger a change of its own
shape moving the bound molecule from one side to the other
- The solute binds to the hydrophobic pocket exposed to one side
of the membrane, the conformational change occurs, this change
withes exposure to other side then solute is released.
- The main pathway for uptake of organic molecules such as sugars,
amino acids, and nucleic acids.
- Types of carriers based on the number of solutes and the
direction of transport are- uniporter: single solute moves in one
direction
 - Symporter- 2 molecules move in the same direction

-Antiporter:
Antiporter: 2 molecules move in opposite directions

https://youtu.be/kK
https://youtu.be/kK-N8jUH5Xs

Movement of particles is faster in channels than in carriers.

2. Active transport
transport:
- The substances move across the membrane with the help of
carrier proteins against the conc. Gradient.
- This method of transport uses cellular energy [ATP hydrolysis ]
- It has two types:
 Primary active transport:
- Involves the function of pump that directly uses energy to
transport a solute against a gradient through carrier proteins
- E.g. antiporter of sodium potassium pump
 Secondary active transport:
- Uses the pre- existing gradient to drive active transport of another
solute
- Also called co-transporter.
- E.g. H+ and sucrose transport- the movement of sucrose
molecules is aided by the energy given by the proton gradient that
was created earlier.

Examples
 Sodium potassium pump:
- This mechanism transports Na+ and K+ through the membrane.
- It is a transmembrane protein complex
- Step1: In the resting stage the carrier is open to the inside of the
cell and it has affinity to Na+ ions and therefore allows 3 Na+ ions
to bind to the pump.
- Step2: The pump gets phosphorylated by ATP which give energy
for the change in the conformation in the pump. This opens the
carrier to the outer region and close it inwards. Now the Na+ ions
move to the outer region. The carrier now gains affinity to K+ ions
and attach 2 K+ ions
- Step3: The pump gets dephosphorylated and the conformation is
as earlier. It opens to the inside and releases the K+ ions inside
- We now have 3 Na + ions out whereas 2K+ ions in, thus making
the outer region more positive than the inner region.
- Concentration : Na+ high out and low in, K+ is high in and low out
- Now K+ moves to the outer region which is against its nature[ +
moving towards +] but along the concentration gradient of K+
ions
- This pumping of 3Na+ and 2K+ accompanied with the movement
of excess K+ ions creates a membrane potential [ approx 70mv]
- This membrane potential is very important for cells. Neurons
spend 2/3 of their energy to maintain their resting membrane
potential.
- This membrane potential helps the cell perform work and
communicate information
  Glucose transport
By facilitated diffusion
- Mediated by GLUTs. These are the uniporters that help in
movement of glucose molecules through the plasma membrane.
- Without enzyme insulin: GLUTs are in the membrane of the
vesicles and few are in the plasma membrane
- With insulin: insulin binds with its receptors on the plasma
membrane and inserts more GLUTs thereby increasing the uptake
of glucose by the cell
- This method is largely used.
By secondary active transport
- Mediated by SGLTs [ sodium dependent glucose transporter]
- The sodium potassium pump creates higher conc. Of Na+ ion
outside the cell [creates an electrochemical gradient}
- The SGLTs use the Na+ ions and binds to glucose and transports it
into the cell
 Bulk transport :
- Macromolecules and large particles are transported via this
method
- Types:
1. Exocytosis: from the cell to the exterior. Examples
- Hormone production: insulin secretion from pancreatic cells
- Digestive enzymes :
- Extracellular matrix: the components of the extracellular matrix is
moved via exocytosis

2. Endocytosis: from outside the cell to in.

- The cell's plasma membrane invaginates, forming a pocket around
the target particle. The pocket pinches off, resulting in the particle
containing itself in a newly created intracellular vesicle formed
from the plasma membrane
- Uptake of vital nutrients that are insoluble in the blood
- In nitrogen fixing roots of leguminous plants the bacteria that
helps in nitrogen fixation is engulfed by endocytosis

3. Phagocytosis:
- The condition of “cell eating”
- The process by which a cell takes in large particles, such as other
cells or relatively large particles.
- The macrophages of our immune system engulf and destroy the
pathogen by phagocytosis

4. Pinocytosis :
- Pinching of water contents from outside to inside
- Called as cell drinking.

5. Receptor mediated endocytosis:

- A targeted variation of endocytosis employs receptor proteins in
the plasma membrane that have a specific binding affinity for
certain substances. E.g. clathrin mediated endocytosis
- A region of the inner plasma membrane becomes coated with the
protein clathrin, which stabilizes this membrane's section.