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BIOLOGICAL
MEMBRANES
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Objectives
Importance
Composition & Models
Important properties
Specialized structures
RBC membrane
Biomembranes
Transport mechanisms
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Importance/ Biological role
Maintenance of shape
Control of movement of molecules across
Cell-cell recognition and communication
Cellular movement
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Chemical composition
Lipids Phospholipids: most predominant
Phosphatidylcholine (lecithin) : 40-50%
Sphingolipids:
Sphingomyelins Glycolipids: 2-10%
Cholesterol: free and esterified absent in prokaryotes
Most rigid lipid in membrane
Proteins Inner mitochondrial membrane contains highest proportion
of proteins
Glycoproteins Carbohydrates do not exist in free form
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Membrane proteins
Enzymatic activity:
Na+ - K+ ATPase pump
Carrier proteins:
Translocases Signal transduction:
IP3 and DAG
Interactions with ECM and cytoskeleton
Fibronectin, Spectrin, Ankyrin Regulation of permeability
Ion channels
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Bound to either face by
electrostatic interactions/
hydrogen bonds
Released by mild
treatment
Salt solution of different
ionic strength pH alteration
Usually enzymes
Removal does not damage
integrity
Embedded deeply
(transmembrane) by
hydrophobic bonds/ van
der Waals force
Removal requires use of
detergents or organic
solvents
Transport proteins
Removal causes
denaturation of protein andloss of function
Peripheral proteins Integral proteins
Membrane proteins
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Lipid bilayer: Models
Amphipathic molecules
Polar heads point outside, Non-polar tails point
inwards
Non-polar core acts as diffusion barrier:
impermeable to polar molecules and ions
1925, Gorter and Grendel proposed lipid
bilayer model 1935, Davson and Danielle suggested
phospholipids as major constituent
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Fluid mosaic model
1972, Singer and Nicholson
Intrinsic proteins immersed in protein bilayer
(60-100A)
Extrinsic proteins loosely attached to surface
of membrane
Charecteristics:
Icebergs in seaNo flip flop
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Fluid mosaic model
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Membrane asymmetry
Proteins are inserted in asymmetric fashion
Oligosaccharide units project towards exterior
Lipids are distributed asymmetrically:
Outer leaflet:
Phosphatidylcholine
Sphingolipids
Inner leaflet: Phosphatidylethanolamine
Phosphatidylserine
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Membrane fluidity
Temperature determine fluidity
Temp : fluidity
Phase transition / melting temperature (Tm)
Composition
Short chain FA fluidity
Cis- Unsaturated FA fluidity (more the no. of double
bonds, the Tm) Cholesterol has dual role
decreases fluidity above Tm
Increases fluidity below Tm by acting like impurity
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RBC membrane
Glycophorin
Integral glycoprotein with oligosaccharide units
facing exteriorly
Determine antigen specificityAnion exchanger
Integral glycoprotein
Extrusion of bicarbonate ions in exchange of
chloride
Ankyrin
Peripheral protein on cytoplasmic side
Cross-linked to spectrin and actin
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Other Biomembranes
Micelles: when critical
concentration of lipids is
present
Liposomes formed by sonication
spheres of lipid bilayers that
enclose aqueous medium.
Clinically useful
carriers of drugs in the
circulation
targeted therapy
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Aquasomes
Most recently developed delivery system
Used for proteins and peptides
Structure: nanoparticulate, three layered, self
assembled
Central solid nanocrystalline core coated with
polyhydroxy oligomers
Biochemically active molecules adsorbed to this core Core gives structural stability and stabilizes active
biological molecules
Used for: Insulin, Hemoglobin, Antigens,
Serratiopeptidase
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Transport across cell
membranes
Lipid bilayers are semipermeable
Non lipid-soluble molecules are handled bymembrane proteins:
Channels for ions/ small mols
Transporters for larger mols
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Lipid-protein association in
membrane
Membrane phospholipids are solvents for
membrane proteins
- helical structures in proteins minimize hydrophilic
character of peptide bonds Proteins are amphipathic
Hydropathy plot
Helps to predict whether a protein can have trans-membrane location
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Specialized membrane
structures
Lipid rafts
Exoplasmic location
Cholesterol, Sphingolipids and proteins
Caveolae
Caveolin-1 protein
Flask shaped indentations in cytosolic side
Tight junctions Prevent diffusion of macromolecules
Located below apical surfaces, between cells
Proteins: occludin, claudins
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Transport processes
Passive diffusion
Carrier mediatedtransport
Facilitated diffusion
Active transport
Primary activetransport
Secondary active
transport Exocytosis and
endocytosis
Transport through
gap junctions
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Passive diffusion
Gases: Highly permeable
Water: Moderately permeable
Ions and large polar molecules: Impermeable
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Carrier-mediated transport
Mediated through integral proteins
Permeases/ Porters/ translocases
Proteins are specific (GLUT)
Can be inhibited by structural analogs
1,5-anhydroglucitol
Uniport
Symport/ Antiport: obligatory simultaneouscotransport of another mol
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Facilitated diffusion
Along concentration gradient, no energy
consumed
Transport protein hastens the process
Mechanism:
oscillation between two conformations: ping-pong
Process is reversible
Kinetics follow Michelis - Menten rate law Egs.
Glucose transporters: GLUT
Chloride transporters: Cl-
/ HCO3-
antiport andc stic fibrosis transmembrane conductance
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Rate kinetics
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Active transport
Solute moves against concentration gradient
Expenditure of energy
Primary active transport:
Energy obtained from ATP hydrolysis: Na-K
ATPase
Secondary active transport:
Substrate molecule moves coupled to another iondown its concentration gradient: Na- glucose
symport
No ATP hydrolysis, energy derived from
electrochemical gradient of the primary ion
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Sodium Potassium
ATPaseSodium Glucose symport
Primary active
transport
Secondary active
transport
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Ion channels
Transmembrane proteins
Selective to certain ions
Allow ionic transport at high rates
Regulated
Types:
Voltage gated
Ligand gated
Mechanically gated
Affected by drugs
T b
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Trans-membrane pore
systems
Small cyclic organic
molecules Shuttles for ions
Eg. Valinomycin and
Gramicidin, used asantibiotics
Tetrameric
transmembraneproteins
Permit passage ofwater only
Mutations causenephrogenicdiabetes insipidus
Ionophores Aquaporins
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Segments of plasmamembraneinvaginate andenclose small vol ofECF
Phagocytosis andpinocytosis
Primary andsecondarylysosomes
LDL mol and
receptor internalized
Release
macromolecules
Involved in
membraneremodelling
Ca++ triggers
exocytosis
Endocytosis Exocytosis
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