IPAM Cells and Materials:
At the Interface between Mathematics, Biology and Engineering
Tutorial 2,
Plasma Membrane
Dr. Toshikazu Hamasaki
Dept. Bioengineering, UCLA
Plasma Membrane
Lipid Bi-layer
Creates Hydrophobic Barrier
Higher Cholesterol contents
(~20%) than Organelle membrane
Glycolipid (external surface of
Plasma Membrane)
Water : Poorly permeable
O2, CO2 : Permeable
Hydrophobic agents (drugs)
Detergent Hydrophobic - Hydrophilic
Plasma Membrane: environmental boundary (barrier)
Electrochemical gradient
Membrane potential
Unique intracellular environment
Stabilize pH
Holds molecules inside
Plasma Membrane: environmental boundary (barrier)
Intracellular Extracellular
(Cytoplasm) (Tissue fluid)
Ion Channels Na+ Na+
10 mM 145 mM
K+ K+
140 mM 4 mM
Pumps
Calcium Calcium
0.1 mM 2 mM
Ca2+ Ca2+
Importers < 0.1 µM 1 mM
Cl- Cl-
Exchangers 3 mM 117 mM
ATP ATP
1 mM < 0.1 µM
Porins
-50 mV
0 mV
Membrane
potential
Ionic imbalance (particularly, Na+ and K+) between inside and outside a cell,
created by membrane ionic pumps, ion exchangers and channels, establishes
resting membrane potential. This is used to drive other process (such as molecule
import), 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.
Plasma Membrane
Components of plasma membrane
Lipids
Phospholipids
Glycolipid
Cholesterol
Proteins; transmembrane proteins, peripheral proteins
Many proteins are glycosylated
Membrane channels, pumps : Ion concentration gradient (inÅÆout)
Membrane potential
Transporters : transport molecule across plasma membrane, e.g. glucose transporter
Membrane receptors : Information relay
(via particular signaling molecules, e.g. hormones, neurotransmitters)
Communication between cells : Gap junctions, integrins
Adhesion molecules (Junctions); cell to extracellular matrix, cell to cell
Endocytosis, Exocytosis : Intracellular membrane flow
Phospholipid structure: e.g. Phosphatidylcholine
cis-double
bond
‘kink’
Mobility of phospholipid
More kinks Î
1. More difficult to pack phospholipid together – membrane stays
fluid at lower temp
(Bacteria, yeast adjust the fatty acid composition according to
temp, to maintain membrane fluidity)
2. The kinks shorten the length of hydrocarbon chains, so that the
membrane is thinner.
Four major phospholipids found in mammalian plasma membrane
There are many ‘minor’ phospholipids exists, too.
(PE) (PS) (PC)
Cholesterol
Unique to plasma membrane
Stabilize membrane
Cholesterol
Unique to plasma membrane
Stabilize membrane
ALSO: Precursor to
steroid hormones
Glycolipids
Unique to plasma membrane
(Extracellular side)
Neutral glycolipid (A)
or,
negatively charged (B)
(due to sialic acid [NANA])
Phospholipid arrangement in Plasma Membrane
Ext. 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)
Lipid Raft
Local area of a
membrane where
sphingolipid,
cholesterol and
membrane proteins are
concentrated.
Plasma Membrane : Membrane Proteins
Functional classification (1)
Transmembrane
Proteins
Plasma Membrane : Membrane Proteins
Functional classification (2)
Transmembrane Proteins
Plasma Membrane : Membrane Proteins
Functional classification (3)
Peripheral Proteins
(only one side of the membrane)
Association of membrane proteins with
the lipid bilayer (1)
Transmembrane Proteins
1. A single α-helix
2. Multiple α-helices
3. Rolled up β-sheet
Association of membrane proteins w/ the lipid bilayer (2)
Peripheral Membrane Proteins
4. α- 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 via
an oligosaccharide linker
7, 8. Noncovalent interaction between
proteins
α helical transmembrane polypeptide chain
Mostly consists of hydrophobic
amino acids (yellow and green)
Hydropathy plot
Prediction of transmembrane α helix by
sequence of amino acids
Seven trans-membrane α helices
Membrane receptor proteins
Signal transduction across the membrane
The signals are used to activate:
gene transcription(s) Æ cell differentiation
cell locomotion
exocytosis / endocytosis
etc
Î Signal Transduction (an another tutorial section)
Overview of membrane transport proteins
These systems exist not only on plasma membrane, but also many organelle membranes.
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. Ca2+ pump
Transporters
ATP-independent systems
(However, Na+ gradient drives Glucose transporter
these transporters;
ATP-driven Na+/K+-pump
generates the gradient.)
Many of the channels, pumps and transporters are
inserted only on particular surface of the cell
Intestinal
epithelial cell
Tight junction serves barriers between apical surface and baso-
lateral surface of plasma membrane (many plasma membrane
proteins, such as channels, pumps, receptors, are inserted only into
one or the other surface of the plasma membrane. These proteins
cannot go (move) across the other side due to tight junction.
Cellular Junctions
Location Each junction consists of specific set
Function of adhesion proteins
Occluding Junctions
Tight Junction
Separates two environments
Paracellular pathway:
Passage through tight
junction b/w cells
Small(er) molecules
water, ions, etc
Occluding Junctions
Tight Junction
Separates two environments
External body <incl. Intestine lumen, urinary-tract lumen>
vs
Extracellular fluid (body fluid) <incl. Blood, lymph>
Tight Junction
Tight Junction :
Separation of Apical vs basolateral
plasma membrane (proteins)
Sealing strands: Plasma-membrane proteins
(Occludin, Claudin)
Visualized with freeze-fracture EM
Ca2+-requirement
Anchoring Junctions:
Adherens Junctions
(Zonula Adherens; Belt Desmosome)
Cadherin
Ca2+-requirement
Anchoring Junctions:
Desmosomes
Maintain strong cell-cell adhesion
Yellow marks: desmosomes Epithelial Cells
Keratin filaments attach cytoplasmic
side of desmosomes
Intercalated Discs
in cardiac muscle
Anchoring Junctions:
Desmosomes
Maintain strong cell-cell adhesion
Focal Adhesion
Cell-Matrix adhesion
Integrin
Cytoskeletal fibers associated:
Actin fibers
– Focal adhesions
– Muscle (lateral) attachment
Intermediate filaments
– Hemidesmosomes
Focal Adhesion
Cell-Matrix adhesion
Hemidesmosome (green)
Cadherin
Integrin
Integrin holds basal lamina
Matrix-binding activity of
Integrin is regulated by
signaling events (below)
e.g. white blood cells
Integrin (cluster) triggers intracellular signalling
Gap Junction
Connexin hexamer (per cell)
‘Connexon’ (hemichannel)
Two connexons from adjacent
cells to form intracellular
channels
Often found as ‘patch’ (cluster)
on a plasma membrane
Gap Junction
Molecules that pass through gap junctions dependent on type of connexons
Molecular size, charge, else?
Examples of GAP-junction-connection between cells
Electrical Synapses (Fishes, Insects etc…)
Cardiac muscle cells / smooth muscle cells
Hepatocytes
Tracheal ciliated epithelial cells [IP3]
Regulation of the channel (Open ÅÆ Close)
Summary of cell-cell / cell-matrix adhesions
Excitatory Properties of Plasma Membrane:
Neuron
Dendrites
Conducts impulses towards
the cell body
Typically short, highly branched
& unmyelinated
Surfaces specialized for contact
with other neurons
(Post-synaptic terminals)
Axons
Conduct impulses away from cell body
Long, thin cylindrical process of cell
Arises at axon hillock
Impulses (Action potentials) arise from
the initial segment (trigger zone)
Side branches (collaterals) end in fine
processes called axon terminals
Synaptic boutons Synaptic end bulbs : contain
vesicles filled with neurotransmitters
Resting Membrane Potential
Nerve cells, (Neurons, Grial cells)
All the other living cells
Potential energy difference at rest is (about) -70 mV
(depending on the cell types)
Establishment of the Resting Membrane Potential
Concentration of ions different; inside & outside the cell
Extracellular fluid: rich in Na+ and Cl-
Cytosol: high [K+], organic phosphate & amino acids
Membrane permeability for Na+ & K+:
50-100 greater permeability for K+
Inward flow of Na+ can’t keep up with outward flow of K+
Na+/K+ pump removes Na+ as fast as it leaks in.
Potential energy difference at rest is (about) -70 mV
Membrane channels (a partial list):
Membrane conductance
Conductance:
Each carried by
specific ion species
Na+, K+, Ca2+
Specific Ion Channels
Depolarization / Hyperpolarization
of the Membrane Potential
Specific ion channels are opened
according to the stimulus
Strength of the stimulus ∝
amount of change in membrane
potential
(Not always; also effective range)
Local change in membrane
potential spreads through
membrane with decay
Depolarization / Hyperpolarization
of the Membrane Potential
Graded Potentials
Source of stimuli
Mechanical 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 potential
Ions flow through ion channels and change membrane potential locally
Amount of change varies with strength of stimuli
Flow of current (ions) occurs only locally
Dendrites and Cell bodies (usually not on axonal membrane)
Action Potential
Produced by voltage-gated ion channels
All – or – None
Voltage threshold
Voltage-gated Na+ Channel
Components of an Action Potential
Voltage-gated Na+ Channel:
Deporalization activated
Voltage-gated K+ Channel
Action Potential
Action potentials start to arise only at trigger zone on axon hillock, in
response to membrane depolarization due to graded potential(s)
generated at dendrites / cell body
Action potential :
enables information processing all-or-none
The refractory period makes action
potential to propagate unidirectional
Propagation of an action potential through an axon
Timing – delays with distance
Slow propagation
Height – remains same
(red arrow)
All – or - None
Myelination of axon and saltatory action potential
conduction at the node of Ranvier
Unmyelinated vs Myelinated axon
Myelinated fibers: appear white jelly-roll
like wrappings
made of lipoprotein = myelin
acts as electrical insulator
speeds conduction of nerve impulses
Unmyelinated fibers: slow,
small diameter fibers
only surrounded by neurilemma
but no myelin sheath wrapping
A myelinated axon, myelin sheath [M] and a
Unmyelinated axones [A] and a schwann cell [S] schwann cell [S]
Saltatory action potential conduction :
Speedup the action potential propagation
