Edge of life
 Separates living cell from its surroundings
 8nm thick means 8000 membranes equal the
thickness of thin page
 Controls traffic into and out of the cell
 Selectively permeable (make fundamentals of
life)
 Membranes form earlier in evolution of life
 They enclose the solution different from its
surroundings.
 Membranes are vital because they separate the
cell from the outside world. They also separate
compartments inside the cell to protect
important processes and events.
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 Made
up of lipids and proteins
 Abundant lipids are phospholipids
 Phospholipid is an amphipathic molecule
having hydrophilic head and hydrophobic tail
 Head consists of choline, phosphate and
glycerol
 Membrane proteins are also amphipathic
having hydrophilic and hydrophobic region
1915:
membranes isolated from RBCs were
chemically analyzed, found to consist of lipids
and proteins
 1925: Two Dutch scientists suggested membranes
are bilayer of phospholipids because they could
exist as stable boundary between two aqueous
compartments
 1930-40: Danielli and Davson studied triglyceride
lipid bilayer over a water surface with the polar
heads facing outward. They always formed
droplets (oil in water) and the surface tension
was much higher than that of cells. However, by
the addition of proteins, the surface tension
was reduced and the membranes flattened out.
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 Surface
of phospholipid bilayer adheres less
strongly to water than the surface of
biological membranes.
 1935: Davson and Danielli suggested that
membranes are coated on both sides with
hydrophilic proteins (Sandwich model)
 1950s EM studies supports sandwich model
 Two problems with sandwich model:
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Membranes with different functions differ in
structure and chemical composition
Proteins dissolve in cytosol but membrane proteins
are not very soluble in water because they are
amphipathic
If amphipathic proteins are layered on the surface of
membrane their hydrophobic part would be in
aqueous surroundings
 1972:
S. J. Singer and G. Nicolson proposed
that membranes proteins reside in the
phospholipid bilayer with their hydrophilic
regions protruding
 This molecular arrangement maximize the
contact of hydrophilic regions of proteins and
phospholipids with water in cytosol and
extracellular fluid
 Membrane is a mosaic of protein molecule
bobbing in a fluid bilayer of phospholipids
 Confirmed by the freeze fracture split
studies of membrane image EM
Four Unit membranes , Two unit membranes form
plasma membrane of each cell
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A technique used to look at membranes that reveal the
pattern of integral membrane proteins.
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General outline of technique:
1. Cells are quickly frozen in liquid nitrogen (19°C), which
immobilizes cell components instantly.
2. Block of frozen cells is fractured. This fracture is irregular
and occurs along lines of weakness like the plasma membrane
or surfaces of organelles.
3. Surface ice is removed by a vacuum (freeze etching)
4. A thin layer of carbon is evaporated vertically onto the
surface to produce a carbon replica.
5. Surface is shadowed with a platinum vapor.
6. Organic material is digested away by acid, leaving a replica
7. Carbon-metal replica is put on a grid and examined by a
transmission electron microscope.
What is the main function of the cell membrane?
 Diverse functions in the different regions and
organelles of a cell. However, at EM level, they
share a common structure
 The cell membrane regulates what enters and
leaves the cell and also provides protection and
support.
 The Lipid Bilayer gives cell membranes a flexible
structure that forms a barrier between the cell
and its surroundings.
 Cell Membrane protein molecules embedded in
the lipid bilayer, some of which have
carbohydrate molecules attached to them.
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Membranes are not static sheets of molecules
 Membranes
molecules
have
hydrophobic
interactions which are much weaker than
covalent bonds
 Lipids and proteins can shift laterally
 Lipids can shift in flip-flop manner from one lipid
layer to another is rare because hydrophilic part
of the molecule has to pass through the
hydrophobic region.
 Lateral movement of phospholipid is rapid.
 Adjacent phospholilipids switch positions about
107 times/sec: 2μm /sec
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Membranes remain fluid as temp decreases until the
phospholipid become closely packed
Solidification temperature depends on the types of
lipids it is made off
Unsaturated hydrocarbons have kinks at double bond
and are more fluid
Saturated hydrocarbons have no double bonds and
tightly packed are less fluid and more viscous
Steroid cholesterol is wedged shaped between
phospholipid of animal cell at 37°C makes the
membrane less fluid by restraining the movement of
phospholipid. It hinders the close packing of
phospholipid therefore lowers the temperature of
membrane solidification (fluidity buffer)
Membranes work better when fluid.
 Solidification:
changes
permeability
and
inactivate enzymatic proteins
 Too fluid membranes can not support the protein
function
 Extreme environments pose a challenge for life
and leads to evolutionary adaptation
 Fishes in extreme cold environment have more
unsaturated phospholipids
 Bacteria at hot springs (90°C) have unusual
phospholipids concentration
 In Winter wheat % of unsaturated phospholipids
increases in autumn
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 Proteins
are mosaic part of membranes
 Diverse proteins exist: 50 kinds of proteins in
RBCs
 Proteins determine most of the functions of
membranes
 Different types of cells contain different sets
of proteins
 Two types:
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Integral proteins: in the hydrophobic interior and
span the membrane
Peripheral protein: not embedded in lipid bilayer
loosely bound on the surface of membrane
 Transport
Proteins: Spans around the
membrane and provide hydrophilic
channel across the membrane. Others
shuttle a substance from one side to the
other by changing shape (carrier protein),
some may hydrolyze ATP as energy source
to actively pump substances across the
membrane
 Enzymatic
activity: A protein in the
membrane may be an enzyme with
its active site exposed to substances
in
adjacent
solution.
Several
enzymes are arranged in series to
carry out the various steps in
metabolic pathways.
 Signal
transduction:
Membrane
protein has binding site of a specific
shape that it fits the shape of
chemical messenger i.e. hormone.
This binding cause a change in the
confirmation of protein to allow it to
relay the message inside cell by
binding the cytoplasmic protein.
(receptor proteins)
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Cell–cell recognition: Glycoproteins of one cell membrane
are recognized by membrane proteins of the other cell. It
is short lived bindings
●Cell-cell recognition is by carbohydrates on the extra
cellular surface of the membrane
● Membrane carbohydrates are short, branched chains of
less than 15 sugar units
● Covalently bond to lipids (glycolipids), and proteins
(glycoproteins)
● Vary from species to species, individuals of same
species, organ to organ, one cell type to other cell of same
species.
● They distinguish one cell from other cell
Example: four blood groups A, B, AB and O are .due to
variation in the carbohydrate of glycoproteins on the
surface of RBCs
 Intercellular
joining: Membrane proteins of
adjacent cells may hook together by various
junctions i.e. gap junctions. Long lasting
binding
 Attachment
to
cytoskeleton
and
extracellular matrix (ECM): Microfilaments
and other elements of cytoskeleton
noncovalently bound to membrane proteins,
maintain the cell shape and stabilize location
of certain membrane proteins. ECM
coordinates extra and intracellular changes
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Cell-cell recognition is by carbohydrates on the extra
cellular surface of the membrane
Membrane carbohydrates are short, branched chains of
less than 15 sugar units
Covalently bond to lipids (glycolipids), and proteins
(glycoproteins)
Vary from species to species, individuals of same
species, organ to organ, one cell type to other cell type
of same species.
They distinguish one cell from other cell
Example: four blood groups A, B, AB and O are .due to
variation in the carbohydrate of glycoproteins on the
surface of RBCs
 Membrane
has distinct inside and outside
faces
 Two lipid layers differ in specific lipid
composition
 Protein has directional orientation in the
membrane
 This sidedness is determined during the
synthesis of membrane by ER and Golgi
apparatus
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Membranes regulate transport across the cellular
boundaries to make their existence
Control the steady traffic of small molecules and ions
in both directions
Chemical exchange between the muscle cell and
extracellular fluid
Sugars, AAs and other nutrients enter the cell and
metabolic products leave it through plasma
membrane
Intake of O2 and expulsion of CO2
Regulate concentrations of inorganic ions Na+, K+, Ca+
and Cl- by shuttling them
Membranes are selectively permeable and regulate
the traffic of substances
 Nonpolar
molecules i.e., hydrocarbons,
CO2 and O2 are hydrophobic can dissolve
in the lipid bilayer of membrane and cross
easily
 Hydrophilic ions and polar molecules are
impeded by the hydrophobic interior
 Polar molecules i-e, water, glucose, other
sugars pass slowly through lipid bilayer
 Charged atoms and molecules cross the
membranes even more slowly
Proteins of the membranes play key roles in
regulating transport
 Channel proteins have hydrophilic channel that
is used as tunnel by certain ions and molecules
 Aquaporins (channel proteins) facilitate the
movement of water molecule across (3billion
molecules/sec) the membrane
 Carrier proteins change the shape according to
specific molecule for shuttling only that
molecule
 i.e., a selective glucose transporter increase the
transport 50,000 times more across membrane
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Selective permeability of
the membrane is
determined by both lipids
and proteins
 Molecules
have thermal energy due to their
constant motion that results in diffusion
 By diffusion the molecules spread evenly in
available space
 Movement of dye molecule through the
synthetic membrane toward water is by
diffusion
 Any
substance will diffuse down its
concentration gradient or from higher
concentration towards lower concentration
 Diffusion is spontaneous process needing no
input of energy
 Uptake
of oxygen by the cell. Dissolved
oxygen diffuses into the cell through plasma
membrane as long as it is consumed by
cellular respiration
 Diffusion of a substance across the biological
membrane is called a passive transport
 Potential energy drives the diffusion
 Selectivity of the biological membranes
control the rate of diffusion of various
molecules depends on the need of cell
 The
diffusion of free water across a
selectively permeable membrane is called
osmosis
 Two
sugar
solutions
of
variable
concentrations are on either side of the
selectively permeable membrane. The pores
of the membrane are so small that only
water molecule can pass not the sugar
molecule
 Water will move from higher concentration
towards lower concentration
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Tonicity is the ability of a surrounding solution to
cause a cell to gain or loose water
Tonicity depends on the concentrations of solutes in a
solution that can not cross the membrane relative to
the inside of cell
If there is higher concentration of solutes in
surrounding solution water will leave the cell or vice
versa
Isotonic solution: no gain or loss of water and cell will
remain same
Hypertonic solution: more solutes out side, cell will
loose water, shrivel and die. i.e. higher salinity of a
lake cause the death of animals
Hypotonic solution: less solutes out side, water will
enter the cell faster than it leaves, the cell will swell
and burst like an over filled balloon
 Sea
water is isotonic to marine animals.
 Terrestrial animal cells live in isotonic
environment.
 Organisms
that lack cell walls have
adaptations
for
osmoregulation.
i.e.
unicellular protist Paramecium caudatum
lives in hypotonic pond water have plasma
membrane less permeable to water. It slowly
uptake the water but does not burst due to
having a contractile vacuole which force
water out of the cell as fast as it enters by
osmosis.
 The
cell of plants, fungi and prokaryotes are
surrounded by walls which help I maintain
the cell’s water balance
 In hypotonic solution protoplasm swells and
exert pressure on the wall in response the
wall exerts pressure called turgor pressure
and cell become turgid
 In Isotonic solution no water enters the cell
and cell become flaccid
 In hypertonic solution the plasma lemma
pulls away from wall and cell become
plasmolysed and become dead
 Many
polar molecules and ions impeded by
the lipid bilayer diffuse passively by
membrane proteins that span the membranes
via facilitated diffusion
 Channel proteins provide corridors to allow
specific molecules or ions to cross the
membrane
 Aquaporin proteins are in high number in
certain kidney cells to reclaim water from
urine before excretion (Absence: 180L
urine/day have to drink equal volume of
water
 Ion
channel proteins: trans port ions
 Gated channel proteins open and close in
response to stimulus (electrical) allowing K+
to leave the cell
 Other gated channel proteins open and close
when specific substance other than the one
to be transported binds to the protein
 Both gated channel proteins are important
in function of nervous system
 Carrier proteins bind and release the
substance by conformational change (Glucose
transporters)
 Active
transport is to pump solutes across
the membrane against its concentration
gradient
 Carrier proteins perform active transport
 Maintains the internal concentration of
solutes of the cell i.e. animal cell has higher
conc. K+ and lower conc. of Na +
 Plasma Membrane maintains steep gradient
by pumping Na+ out of the cell and K+ in cell
 ATP supplies the energy for active transport
by transferring its terminal phosphate group
 Example is Sodium Potassium pump: 3 Na+
leave the cell and 2 K+ enters the cell
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Cells have voltages across the plasma membranes
Voltage is electrical potential energy
Cytoplasmic side is negatively charge relative to
extracellular side due to an unequal distribution of
ions and cations on both sides
Voltage across the membrane is called membrane
potential (ranges -50 to -200 mV)
Membrane potential affects the traffic of all charged
substances across the membranes
Inside of cell is negative compared with out side the
membrane potential favors the passive transport of
cations into the cell and anions out of the cell
Chemical force (ion’s conc. gradient) and electrical
force (membrane potential) act together is called
electrochemical gradient
Ions diffusion is down to its electrochemical gradient
 i.e.
[Na+] inside the resting nerve is much
lower than out side it. Upon cell’s
stimulation channel opens that facilitate Na +
diffusion. Na+ fall down their
electrochemical gradient driven by [Na+] and
by the attraction of these ions to negative
side (inside) of membrane
 Na+/K+ pump translocate 3 Na + outside and 2
K + inside the cell in one crank of cycle and
stores energy as voltage
 Transport protein generates voltage across a
membrane is called electrogenic pump i.e.
Na/K pump in animal cell and proton pump
in plants, fungi and bacteria that pumps H +
 Proton
pump transfers H + out side the plasma
membrane in extracellular solution
 Generates voltage across the membranes
 Electrogenic pumps store energy that can be
tapped for cellular work
 Proton gradient is used for ATP synthesis
during cellular respiration
A single ATP-powered pump that transport a
specific solute can indirectly drive active
transport of other solutes is called cotransport
 A cotransporter protein separate from H+ pump
drives the active transport of amino acids,
sugars, several other nutrients into cell. i.e.
sucrose-H+ transporter
 Sucrose-H+ cotransporter load sucrose produced
by photosynthesis into leaf veins
 During diarrhea cotransporter of colon reabsorb
Na from waste to maintain constant level in the
body but diarrhea expels waste so rapidly that
reabsorption is not possible and Na level falls .
 For treatment salt and glucose is given which is
picked up by intestinal cotransporter and pass in
the blood.
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 An
antiporter (counter-transporter) is an
integral membrane protein involved in 2°
active transport of two or more different
molecules or ions across a phospholipid
membrane
 In 2° active transport, one species of solute
moves along its electrochemical gradient,
allowing a different species to move against
its own electrochemical gradient
 Example, the Na+/Ca2+ exchanger removes
cytoplasmic calcium, exchanges one calcium
ion for three sodium ions.
 Exocytosis
is the secretion of biological
molecules by fusion of vesicles with plasma
membranes
 Golgi vesicles carrying substances move to
the plasma membrane and fuses its
membrane with PM and content of the
vesicle spills outside the cell
 i.e. cells in pancrease secretes insulin
extracellularly by exocytosis. Neurons
release neurotransmitters by exocytosis that
signals other neurons or muscle cells.
 i.e. Plant cell wall synthesis is by exocytosis
 In
take of biological molecules and particles
by forming vesicles from plasma membrane is
called endocytosis
 A small area of plasma membrane sinks
inward to form a pocket which deepens and
pinches in forming vesicles containing
extracellular material
 Three types of endocytosis:
1. Phagocytosis (cellular eating)
2. Pinocytosis (cellular drinking)
3. Receptor mediated endocytosis
Phagocytosis: a cell engulfs a particle wrapping
pseudopodia around it and packaging like a food
vacuole. Particle will be digested after lysosomal
fusion with it.
 Pinocytosis: a cell gulps droplets of extracellular
fluid into tiny vesicles.
 Receptor-mediated endocytosis: a cell aquire
bulk quantities of specific substances embedded
in the membrane are proteins with specific
receptor site exposed to exterior fluid from
where ligands bind. The receptor proteins
cluster in region of membrane called coated pits
which are lined on exterior by coat proteins. The
ingested material is liberated out and receptors
recycled to plasma membrane by same vesicle
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