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Tutorial 2,Tutorial 2,Plasma MembranePlasma Membrane
IPAM Cells and Materials:IPAM Cells and Materials:
At the Interface between Mathematics, Biology and EngineeringAt the Interface between Mathematics, Biology and Engineering
Dr. Toshikazu HamasakiDr. Toshikazu Hamasaki
Dept. Bioengineering, UCLADept. Bioengineering, UCLA
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Plasma Membrane
Lipid Bi-layerCreates Hydrophobic BarrierHigher Cholesterol contents
(~20%) than Organelle membraneGlycolipid (external surface of
Plasma Membrane)Water : Poorly permeableO2, CO 2 : PermeableHydrophobic agents (drugs)Deter ent H dro hobic - H dro hilic
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Plasma Membrane: environmental boundary (barrier)Electrochemical gradient
Membrane potentialUnique intracellular environment
Stabilize pHHolds molecules inside
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Plasma Membrane: environmental boundary (barrier)
Ionic imbalance (particularly, Na + and K +) between inside and outside a cell,created by membrane ionic pumps, ion exchangers and channels, establishesresting membrane potential. This is used to drive other process (such as moleculeimport), as well as for information processing ( e.g. nerve cells).Activities of plasma membrane ionic pumps are energized by hydrolysis of ATP.
All the live cells establish and maintain the membrane potential.
-50 mV
0 mV
Na + Na +10 mM 145 mMK + K+
140 mM 4 mM
Calcium Calcium0.1 mM 2 mMCa 2+ Ca 2+
< 0.1 M 1 mMCl - Cl -3 mM 117 mM
ATP ATP1 mM < 0.1 M
Intracellular Extracellular(Cytoplasm) (Tissue fluid)
Membranepotential
Ion Channels
Exchangers
Pumps
Importers
Porins
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Plasma MembraneComponents of plasma membrane
LipidsPhospholipids
GlycolipidCholesterol
Proteins; transmembrane proteins, peripheral proteinsMany proteins are glycosylated
Membrane channels, pumps : Ion concentration gradient (in out)
Membrane potentialTransporters : transport molecule across plasma membrane, e.g. glucose transporterMembrane receptors : Information relay
(via particular signaling molecules, e.g . hormones, neurotransmitters)Communication between cells : Gap junctions, integrinsAdhesion molecules (Junctions); cell to extracellular matrix, cell to cellEndocytosis, Exocytosis : Intracellular membrane flow
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Phospholipid structure: e.g. Phosphatidylcholine
cis -doublebondkink
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More kinks
1. More difficult to pack phospholipid together membrane staysfluid at lower temp(Bacteria, yeast adjust the fatty acid composition according totemp, to maintain membrane fluidity)
2. The kinks shorten the length of hydrocarbon chains, so that themembrane is thinner.
Mobility of phospholipid
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Four major phospholipids found in mammalian plasma membrane
(PE) (PS) (PC)
There are many minor phospholipids exists, too.
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Cholesterol
Unique to plasma membraneStabilize membrane
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CholesterolUnique to plasma membrane
Stabilize membrane
ALSO: Precursor tosteroid hormones
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Glycolipids
Unique to plasma membrane(Extracellular side)
Neutral glycolipid (A)or,
negatively charged (B)
(due to sialic acid [NANA])
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Phospholipid arrangement in Plasma MembraneExt. Cellular Side:two unique lipids
Glycolipids (blue)Sphingomyelin (brown)
Cytospsmic Side:PS [negatively charged]PE
Cholesterol (not shown)
are found in both side.
(PE) (PS) (PC)
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Lipid Raft
Local area of amembrane wheresphingolipid,cholesterol andmembrane proteins areconcentrated.
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Plasma Membrane : Membrane ProteinsFunctional classification (1)
TransmembraneProteins
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Plasma Membrane : Membrane ProteinsFunctional classification (2)
Transmembrane Proteins
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Plasma Membrane : Membrane ProteinsFunctional classification (3)
Peripheral Proteins(only one side of the membrane)
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Association of membrane proteins withthe lipid bilayer (1)
Transmembrane Proteins
1. A single -helix2. Multiple -helices3. Rolled up -sheet
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Association of membrane proteins w/ the lipid bilayer (2)Peripheral Membrane Proteins
4. - helix (hydrophobic face)embedded in the lipid bilayer
5. Protein covalently attaches lipid chain fatty acid chain or prenyl group(cytoplasmic side)
6. Protein attaches phosphatidylinositol viaan oligosaccharide linker
7, 8. Noncovalent interaction betweenproteins
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helical transmembrane polypeptide chainMostly consists of hydrophobic
amino acids (yellow and green)
Seven trans-membrane helices
Hydropathy plotPrediction of transmembrane helix bysequence of amino acids
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Membrane receptor proteinsSignal transduction across the membrane
The signals are used to activate:
gene transcription(s) cell differentiationcell locomotionexocytosis / endocytosis
etc
Signal Transduction (an another tutorial section)
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These systems exist not only on plasma membrane, but also many organelle membranes.Overview of membrane transport proteins
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Na + /K +-ATPase (Na + /K +-pump)1 ATP used for exporting 3 Na + ions and importing 2 K + ions.Crucial for maintaining resting membrane potential.
Other pumps; e.g. Ca 2+ pump
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Transporters
ATP-independent systems(However, Na + gradient drives
these transporters;ATP-driven Na + /K +-pump
generates the gradient.)
Glucose transporter
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Many of the channels, pumps and transporters areinserted only on particular surface of the cell
Intestinalepithelial cell
Tight junction serves barriers between apical surface and baso-lateral surface of plasma membrane (many plasma membraneproteins, such as channels, pumps, receptors, are inserted only into
one or the other surface of the plasma membrane. These proteinscannot go (move) across the other side due to tight junction.
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Cellular JunctionsLocationFunction
Each junction consists of specific setof adhesion proteins
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Occluding JunctionsTight Junction
Separates two environments
Paracellular pathway:Passage through tight junction b/w cells
Small(er) moleculeswater, ions, etc
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Occluding JunctionsTight Junction
Separates two environments
External body vs
Extracellular fluid (body fluid)
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Tight JunctionTight Junction :
Separation of Apical vs basolateralplasma membrane (proteins)
Sealing strands: Plasma-membrane proteins(Occludin, Claudin)Visualized with freeze-fracture EM
Ca 2+-requirement
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Adherens Junctions(Zonula Adherens; Belt Desmosome)
Ca2+
-requirement
Cadherin
Anchoring Junctions:
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Desmosomes
Yellow marks: desmosomesKeratin filaments attach cytoplasmic
side of desmosomes
Epithelial Cells
Intercalated Discsin cardiac muscle
Maintain strong cell-cell adhesion
Anchoring Junctions:
h i i
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DesmosomesMaintain strong cell-cell adhesion
Anchoring Junctions:
F l Adh i
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Focal Adhesion
Integrin
Cytoskeletal fibers associated:Actin fibers
Focal adhesions Muscle (lateral) attachment
Intermediate filaments Hemidesmosomes
Cell-Matrix adhesion
F l Adh i
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Focal AdhesionCell-Matrix adhesion
CadherinIntegrin
Hemidesmosome (green)
I t i h ld b l l i
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Integrin holds basal lamina
Matrix-binding activity of Integrin is regulated by
signaling events (below)e.g. white blood cellsIntegrin (cluster) triggers intracellular signalling
Gap J nction
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Gap JunctionConnexin hexamer (per cell)
Connexon (hemichannel)Two connexons from adjacentcells to form intracellularchannels
Often found as patch (cluster)on a plasma membrane
Gap Junction
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Gap JunctionMolecules that pass through gap junctions dependent on type of connexons
Molecular size, charge, else?
Examples of GAP-junction-connection between cellsElectrical Synapses (Fishes, Insects etc)Cardiac muscle cells / smooth muscle cellsHepatocytesTracheal ciliated epithelial cells [IP 3]
Regulation of the channel (Open Close)
Summary of cell cell / cell matrix adhesions
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Summary of cell-cell / cell-matrix adhesions
Excitatory Properties of Plasma Membrane:
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Excitatory Properties of Plasma Membrane:Neuron
DendritesConducts impulses towardsthe cell body
Typically short, highly branched& unmyelinatedSurfaces specialized for contact
with other neurons(Post-synaptic terminals)
AxonsConduct impulses away from cell bodyLong, thin cylindrical process of cellArises at axon hillock
Impulses (Action potentials) arise fromthe initial segment (trigger zone)Side branches (collaterals) end in fine
processes called axon terminals
Synaptic end bulbs : containvesicles filled with neurotransmittersSynap ti c bou to ns
Resting Membrane Potential
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Nerve cells, (Neurons, Grial cells)All the other living cells
Potential energy difference at rest is (about) -70 mV(depending on the cell types)
Resting Membrane Potential
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Membrane channels (a partial list):
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Membrane channels (a partial list):Membrane conductance
Conductance:Each carried byspecific ion speciesNa +, K +, Ca 2+
Specific Ion Channels
Depolarization / Hyperpolarization
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Specific ion channels are openedaccording to the stimulus
Strength of the stimulus amount of change in membrane
potential(Not always; also effective range)
Local change in membranepotential spreads throughmembrane with decay
Depolarization / Hyperpolarizationof the Membrane Potential
Depolarization / Hyperpolarization
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Graded Potentials
Source of stimuliMechanical stimulation of membranes with mechanical gated
ion channels (pressure)Chemical stimulation of membranes
with ligand gated ion channels (neurotransmitter, hormone)
Graded/postsynaptic/receptor or generator potentialIons flow through ion channels and change membrane potential locallyAmount of change varies with strength of stimuli
Flow of current (ions) occurs only locallyDendrites and Cell bodies (usually not on axonal membrane)
Depolarization / Hyperpolarizationof the Membrane Potential
Action Potential
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Produced by voltage-gated ion channels
All or NoneVoltage threshold
Voltage-gated Na + Channel
Components of an Action Potential
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p
Voltage-gated Na + Channel:Deporalization activated
Voltage-gated K + Channel
Action Potential
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Action potentials start to arise only at trigger zone on axon hillock, inresponse to membrane depolarization due to graded potential(s)generated at dendrites / cell body
Action potential :bl f ll
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enables information processing all-or-none
The refractory period makes actionpotential to propagate unidirectional
Propagation of an action potential through an axon
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Timing delays with distance
Slow propagationHeight remains same
(red arrow)All or - None
p g p g
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Unmyelinated vs Myelinated axon
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A myelinated axon, myelin sheath [M] and aUnmyelinated axones [A] and a schwann cell [S] schwann cell [S]
Myelinated fibers: appear white jelly-rolllike wrappingsmade of lipoprotein = myelin
acts as electrical insulatorspeeds conduction of nerve impulses
Unmyelinated fibers: slow,small diameter fibers
only surrounded by neurilemmabut no myelin sheath wrapping
Saltatory action potential conduction :
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Saltatory action potential conduction :Speedup the action potential propagation