MEMBRANES: STRUCTURE AND
FUNCTION
TOPIC 4
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BIOMEDICAL IMPORTANCE
• Plasma membranes- form closed compartments around cellular
protoplasm to separate one cell from another
• Selective permeabilities- provided by channels and pumps for ions and
substrates
• Receptor property
• Exchange materials with extracellular environment – excocytosis and
endocytosis
• Gap juctions
• Cell-cell interactions
• Transmembrane signaling
• Form specialized compartments within cell – provide shape for mitoch, ER,
golgi
• Membrane localize enzymes-excitation response coupling• Site for energy transduction
• Changes in membrane structure?
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Maintenance of a normal intra&extracellular environment is fundamental
to life
Life originated in aqueous environmentsenzyme reactions, cellular and subcellular
processes evolved to work in this milieu.
How this aqueous state is maintained?
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Fluid distribution
2 large compartments that distribute water
1. Intracellular fluid – ICF
• 2/3 of body water
• Provides the environment for the cell
 to make, store and utilize energy
 to repair itself
 to replicate
 to perform special functions
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Fluid distribution
2. Extracellular Fluid –ECF
• 1/3 of body water
• A delivery system for glucose, f.a, a.a, O2, ions
and trace minerals etc
• Remove CO2 and waste product from cellular
environment
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The ionic compositions of intracellular and
extracellular fluids
Mammalian cell maintained the ionic
compositions through the membranes
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Membranes structure
Lipids, Proteins and
Carbohydrates
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MEMBRANES MODEL
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LIPIDS COMPOSITION IN MEMBRANE
• Major lipids – phospholipids, glycosphingolipids
& cholesterol
amphipatic
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Membrane lipids form bilayer
• Bilayers- a structure formed
resemble the micelle structure
– provide optimal condition
for amphipatic molecules
• Hydrophobic regions are
protected from the aqueous
environment and hydrophilic
regions are immersed in water
• Micelles can only extedn to
200nm – and bilayers can
extend to 1mm
• Formed by self-assembly –
driven by the hydrophobic
effect
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Lipid bilayer
How many biologic materials are lipid soluble and can
therefore readily enter the cells?
•O2, CO2, N2- readily diffuse
•Other molecules (Figure)
diffuse according their
permeability in non polar
solvents
•Steroids more readily
traverse the lipid bilayer
compared with electrolytes
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Lipid bilayer
How molecules that are non lipid-soluble cross
the membrane?
• Membrane contain protein – form channels for the
movement of ions and small molecules
• Serve as transporter for larger molecules
• Different membrane consist of different composition
of protein
• Include – enzymes, pumps and channels, structural
components, antigen (for MHC), and receptor for
various molecules
• 2 types of proteins – integral and peripheral
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Integral protein
• Deeply embbedded in the
membrane
• Span the bilayer
• Usually globular and amphipatic
• Certain protein (transporter,
receptor, G proteins) – span the
bilayer many times
• Asymmetrically distributed across
the membrane bilayer
• Require detergent or their
solubilization
• Eg: insulin receptor, glycophorin,
rhodopsin
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Peripheral protein
•
Do not interact directly with
phospholipids in the bilayer- don’t need
detergents for their release
•
Bound to charge group of lipid bilayer
•
Attach to the integral protein or
penetrate the peripheral regions of lipid
bilayer
•
Can be released by treatment with salt
solutions
•
Eg- enzyme (phosphilipases,
glycosyltransferases and many more!
•
Transportr of small hydrophobic
molecules-glycolipid transfer protein,
sterol carrier protein
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Fluid Mosaic Model
• Proposed by Singer and Nicholson
• Resemble to icebergs (membrane
protein) floating in a sea of
predominantly phospholipid
molecules
• Integral protein and phospholipid
were found rapidly and randomly
redistributed in the plasma
membrane-fluidity
• Fluidity- depends on the lipid
composition of the membrane
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Fluid Mosaic Model
•
Unsaturated-have kink in
the hydrocarbon chaincause disorder in the
packing of the chains-more
open structure and fluid
• Saturated f.a –no kink and
have longer hydrocarbon
chain – interact more
strongly –more rigid
structure
• Cholesterol-enhance order
and rigidity
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Effect of temperature
• Temperature increase- hydrophobic side
chains undergo a transition from an ordered
state (gel like) to a disordered state (fluid)
• Transition temperature
• The longer and saturated the hydrocarbon
chains- the higher temperature needed to
increase the fluditiy
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Membrane fluidity
The fluidity of membrane affect its functions
• Fluidity ↑- permeability to water and other small
hydrophilic molecule ↑-lateral mobility of integral
protein ↑
• active site in hydrophilic region maybe affected
• if protein involve in transportation, location changes
cause disruption in transportation
Eg. Insulin receptor
↑ in unsaturated f.a cause ↑ in fluidity- alter the
receptor so it binds more insulin (pls check)
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Membrane Selectivity
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TYPE OF TRANSPORT MECHANISM
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Active and Passive transport
• Passive – do not involve energysubstance move from ↑ conc
to ↓ conc – in the same
direction as conc gradient
• Active – substance moves from
↓ conc to ↑conc – against
conc gradient – require energy
• Passive – simple diffusion and
facilitated
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Passive transport
Factors affect diffusion of a substance:
1. Conc gradient across the memb
2. The electrical potential across the memb – solutes move
toward the solution that has the opposite charge – inside of
cell has a neg charge
3. The permeability coefficient of the substance for the memb
4. The hydrostatic pressure gradient across the memb ↑pressure will ↑the rate and force of the collision between
the molecules and memb
5. Temperature -↑ temp will↑ the freq of collisions between
external particles and the memb
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Passive transport- simple diffusion
• Small, uncharged
molecules, such as O2,
N2, and C02
• Rate of movement
depend on the conc
difference across the
membrane
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Active transport
• Identified by the presence of carrier protein
• The need for an energy source to move
solutes against a gradient
• Primary active transport-linked to hydrolysis
of energy – pumping water uphill -E.g sodiumpotassium pump
• Secondary active transport –e.g- galactosidase
permease in cell
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Transport system
• Uniport system-move one type of
molecule bidirectitonally
• Co transport system-transfer of
one solute depends upon the
stoiciometric simultaneous or
sequential transfer of another
solute
• Symport – moves these solutes in
the same direction –eg: protonsugar transporter in bacteria and
Na+ - sugar transporter and Na+amino acid transporters in
mammalian cells
• Antiport-moves 2 molecules in
opposite directions. Eg.Na+ in
and Ca2+ out
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Passive transport- facilitated diffusion
• Uniport system
• Using carrier protein
• Glucose pass thru the
membrane using
glucose permease as
the carrier protein
• No energy is expended
• E.g. Ping-Pong
mechanism
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Passive transport- facilitated diffusion
• Hormones regulate facilitated diffusion by
changing the number of transporters available
• Insulin increases glucose transport from
intracellular reservoir
• Glucocorticoid hormones-enhance transport
of aa into liver
• Growth hormon-increase amino acid transport
in all cells
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Transport System
1.
2.
3.
4.
Ion channels
Ionophores
Water channels (Aquaporins)
Gap Junction
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ION CHANNELS
• Ion channelstransmembrane, pore like
structure composed of
proteins
• Specific channels for Na+,
K+. Ca2+ and Cl- have
been identified
• Open transiently and thus
gated – can be controlled
by opening and closing
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ION CHANNELS
• Ligand-gated channels- specific
molecule binds to a receptor and
opens the channelneurotransmitter
• Voltage-gated channels-open or
close in response to changes in
membrane potential- activated by
changes in electrical potential
difference – neuron and muscle
tissue
• Example of active transport using
ion channels – Sodium Potassium
Ion Pump and Galactose
Permease
Visit Youtube for animation
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Sodium Potassium Ion Pump
• Under normal condition, ([K+]inside
> [K+] outside) and ([Na+]inside <
[Na+] outside)
• Energy required to move these
ions against their gradients
comes from hydrolysis of ATP
• The protein function as enzyme
that hydrolyze ATP and as
transporter- ATPase
• The pumping process transport 3
Na+ ions out of the cell for every
2 K+ ions transported in the cell
• Self-study: Details mechanism
involve in Na+K+ pump
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Galactose Permease
• In bacteria
• [lactose]inside the bacterial
cell>outside – moving lactose into the
cell req energy
• Galactose permease does not directly
hydrolyze ATP-but harnesses the
energy by using the higher
concentration of H+ outside cell to
drive the conc of lactose inside cell
• Self-study: Details mechanism
involve in Na+K+ pump
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Ionophores
• Synthesize by microbes that
fx for the movement of ions
across membrane
• Microbial toxin-diphteria
toxin can produce large
pores in cellular
membranes-get access to
internal milieu
• Two types:
1. Mobile ion carriers –
Valinomycin (refer uncouplers
of oxidative phosphorilation)
2. Channel formers - gramicidin
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Aquaporins
• A water channel to transport
water
• Red cell and cell of the
collecting ductules of the
kidney-movement of water
through water channelaquaporins
• 5 distinct aquaporins (AP-1 to
AP-5)
• Mutations in gene encode for
AP-2- nephrogenic diabetes
insipidus
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Transmembrane signalling
• Producing the effect of biologically active
substance – substance need to bind to a
protein receptor site on the exterior of cell
• Resemble enzyme-substrate recognition
• Eg for protein receptor for Low density
lipoprotein (LDL).
• LDL- protein, cholesterol and
phosphoglycerides
• Protein bind to receptor- pinched off into
the cell (endocytosis)
• Cholesterol is used in the cell
• The receptor is recycled back to the
surface of cell
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• A process by which cells take up
large molecules
(polysachharide,proteins,
polynucleotide)-forming vesicles
Endocytosis
• The molecules are digested to yield
aa, simple sugars and nt – diffuse
out of vesicles to be reused in
cytops
• Require ATP, Ca2+ in extracellular
fluid and contractile elements
(microfilament)
• 2 types: phagocytosis-in specialized
cell (mphage and granulocytes) –
ingestion large particles (virus,
bacteria, cells, debris)
• Pinocytosis – fluid phase and
absorptive pinocytosis
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Phagocytosis
• Engulfment of large particles –
viruses, bacteria, cell, debris
by macrophages and
granulocytes
• Pseudopodia will surround the
particles and for phagosome
• Phagosome will fuse with
lysosome forming
phagolysosomes –particles are
digested
• Macrophage are extremely
active and may ingest 25% of
their volume per hour
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Exocytosis
• Process of of excreting
macromolecules outside cells
• Molecules can attach to the
cell surface and become
peripheral proteins – antigen
• They can become part of
extracellular matrix- collagen
and glycosaminoglycans
• Can enter extracellular fluid
and signal other cells –
insulin, parathyroid hormone
and catecholamines-to be
released upon appropriate
stimulation
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Pinocytosis
• Absorption of
extracellular fluid from
outside by formation of
small vesicles
• The cell take in all
surrounding fluids and
including all solutes
present
• ‘Cell drinking’
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Gap junctions
• Specialized regions on the
membranes of individual
cells for intercellular
communication in close
proximity
• Mediate and regulate
passage of ions and small
molecules (10002000MW) through a
narrow hydrophilic core
connecting cytosol of
adjacent cell-connexin
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TASK
1. Discuss the effect of abnormalities of cell membrane fluidity.
State example of disease and explain how the disease
develop
2. Discuss the medical applications of membrane in drug
delivery system
3. Discuss disease related to defective phagocytosis in animal
4. Disease related to receptor mediated endocytosis
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