Download IB104 - Lecture 9 - Membranes Introduction The phospolipid bilayer

There have been many magnificent “boats” built to try to reach 50 knots.
This was the creation of an Australian team that held the record for more
than a decade, from 1993 till 2005, at 46.5 knots with their “solid wing”
sail rigged on three planning pods, called Yellow Pages Endeavour.
IB104 - Lecture 9 - Membranes
Reading - Chapter 5
Introduction
1. A membrane surrounds the entire cell - the cell or plasma membrane.
2. Membranes also surround the nucleus, mitochondria, cytomembrane
system, lysosomes, and all other intra-cellular organelles.
3. Thus membranes determine how cells interact with their environment,
including other cells.
4. They also determine how organelles interact with the cytoplasm.
5. Their basic structure is a phospholipid bilayer with embedded
proteins.
6. The phospholipid bilayer provides the basic properties of selective
permeability.
7. The embedded and associated proteins provide additional functions
ranging from movement of ions across the membrane to perception of
light and chemicals to endocytosis of large molecules.
2. Phospholipids therefore spontaneously form spheres of phospholipid
bilayers in water.
The hydrophobic lipid tails interact with each other, excluding water.
The hydrophilic phosphate heads interact with water on either side.
The phospolipid bilayer
1. Plasma/cell and organelle
membranes are all phospholipid
bilayers.
A phospholipid is a triglyceride with
one of the fatty acids replaced with a
complicated phosphate group.
Fatty acids are hydrophobic, while
the phosphate group is hydrophilic.
Thus phospholipids are
amphipathic, wanting to interact
both with water and each other.
Cholesterol has similar amphipathic
characteristics, and hence generally
resides within membranes.
H2O
Cholesterol (sterol)
H2O
Phosphatidylcholine
(phospholipid)
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3. Phospholipid bilayers are selectively permeable.
They are permeable to small non-polar molecules, most famously
oxygen and carbon dioxide, as well as lipid-soluble molecules.
They are impermeable to large, or polar, or charged molecules, e.g. ions.
oxygen, carbon dioxide, glucose and other large, polar,
and other small, nonpolar water-soluable molecules; ions
molecules!
(e.g., H+, Na+, K+, CA++,
CI–); water molecules!
5. Osmosis is the process whereby water moves across a membrane to
equalize the concentrations of ions and other solutes on either side of the
membrane.
For example, cells will
swell in distilled water,
and shrink in salt water.
2% sucrose
solution
Drink companies like
Gatorade sell “isotonic”
drinks.
distilled water
10%
sucrose
solution
2%
sucrose
solution
Hypotonic
Conditions
Hypertonic
Conditions
Isotonic
Conditions
4. Diffusion of water across cell membranes is strange. A pure
phospholipid bilayer is impermeable to water, however water readily
moves across real cell membrane. Instead water crosses through
specialized water channel proteins called aquaporins. Klaus Schulten in
Biophysics generated the image on the left below, showing blue water
molecules crossing the membrane (pink region) through such a water
channel made up of multiple aquaporins (a single one is on the right).
Dealing with the differences between salty and fresh water has serious
consequences for many fish that move been these two kinds of habitats.
Most famously, salmon smolts leaving their river birthplaces spend
weeks adjusting to the ocean, while returning adults must spend several
days in the brackish water at river mouths adjusting their physiology.
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The embedded proteins
1. Each has at least one stretch of ~20 hydrophobic amino acids that
form an alpha helix to cross the phospholipid bilayer and embed in the
membrane. They can move fairly freely around within the membrane.
passive
transporter
recognition
protein
receptor
protein
high
lipid
bilayer
cytoskeletal
proteins
cytoplasm
active transporter active transporter
(calcium pump)
(ATPase pump)
The opening and closing of these channels is regulated so that ions can
only diffuse down their concentration gradient when the relevant
channel is open - this is facilitated diffusion or passive transport.
For example, in nerve cells, an electric signal is transmitted by first
opening sodium channels to allow sodium ions to diffuse into the cell
down their established concentration gradient, followed by opening of
potassium channels allowing potassium ions to diffuse out of the cell
shortly thereafter.
3. Sometimes ions must be moved against their concentration gradient, in
which case this is active transport. This requires energy in the form of
ATP. Concentration gradient
adhesion
protein
2. In addition to the aquaporins or water channels, there are many other
channel proteins that facilitate movement of impermeable molecules
across membranes. Your textbook calls this passive transport.
The best known are the various specific ion channels, e.g. for sodium,
potassium, and calcium ions in nerve cells (Na+, K+, Ca++).
ATP
low
Diffusion of
lipid-soluble
substances
Passive transport
of water-soluble
substances
Active transport
through ATPase
In nerve cells there is a
spectacular protein called
the sodium/potassium
pump, which couples active
transport of a sodium ion
out of the cell with transport
of a potassium ion into the
cell, both against their
concentrations gradients,
but without creating an
electrical gradient.
Donation of a phosphate
from ATP to the protein
drives the first step; removal
of the phosphate from the
protein drives the second
step.
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4. Cystic fibrosis is a unusually common genetic disease involving
failure of chlorine ion transport across membranes.
The cause is a mutation in a type of transporter known as CFTR, for
cystic fibrosis transporter/receptor.
While there are many possible mutations that can inactivate CFTR, a
particular mutant, in which one amino acid of the ~1500 aas in the
protein is missing, is particularly common in Caucasians.
Failure of chlorine transport causes a variety of problems, but most
importantly build up of mucous in the lungs, which allows infection
with bacteria, especially Pseudomonas aeruginosa, which can eventually kill.
Read the intro to chapter 5 for more.
5. All large molecules must be actively transported across membranes,
e.g. the glucose transporter. A change in the shape or conformation of
the protein moves a glucose molecule across the membrane. There are
hundreds of different transporters for different molecules.
6. Receptors interact with molecules outside cells and send signals
inside cells. The internal signal is commonly cyclic AMP.
For example, opsins are receptors that can perceive light. These proteins
have seven transmembrane domains. Many similar proteins recognize
all sorts of hormones, and I work on the chemoreceptors of insects and
nematodes, which like us have hundreds to thousands of different
chemoreceptors to detect all the chemicals they and we smell and taste.
7. Cell adhesion proteins
interact with surfaces or with
proteins on other cells, indeed
commonly these are homophilic
interactions, meaning that the
extracellular part of an
adhesion protein interacts
within other copies of itself on
neighboring cells, thereby
holding them all together in a
tissue. The intracellular part of
these proteins generally binds
to components of the
cytoskeleton, making the
adhesion strong. This diagram
shows one example, a
cadherin, but there are many of
these adhesion proteins.
!
solute (glucose)!
high
glucose transporter!
low
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9. Viruses commonly take advantage of the embedded proteins in cell
membranes to attach to and enter cells. These proteins are sometimes
called viral receptors, but this is inappropriate as they all have useful
functions in cells, the viruses are just exploiting them. E.g. HIV attaches to two proteins on specific white blood cells. The few
people who are resistant to HIV infection and hence AIDS are mutant for
one or other of these two receptors (neither of which is essential to live).
8. Recognition proteins
provide a means for
differentiating “self” from
“non-self”. As you will see
later, this is particularly
important for the immune
system and generally prevents
our adaptive immune system
from attacking our own cells
and tissues. Many terrible
diseases involve failure of this
step, e.g. juvenile diabetes and
arthritis.
Outside
These recognition proteins must be highly variable and there are many of
them, making the “repertoire” of any individual different from any other
individual. The major ones are called HLAs, e.g. above, and can bind
foreign peptides (yellow) and present them to the immune system (TCR).
10. Endocytosis is a
receptor-mediated method
for bringing large
molecules into cells. Pits
endocytotic
lined with receptors
vesicle
linked to a protein called
clathrin form on cell
membranes, and
eventually invaginate and
pinch off, bringing the
bound molecules into
vesicles inside the cell.
These vesicles can
interact with lysosomes
and other intra-cellular
vesicles like the Golgi
body.
Cell membrane
Inside
11. Phagocytosis is the process whereby cells envelop and ingest other
cells, for example, amoebae or white blood cells eating bacteria. Once
engulfed and surrounded by a part of the cell membrane that buds off as
a vesicle inside the cell, the bacteria are digested by protein enzymes in a
lysosome with which the vesicle has fused.
clathrin
exocytotic
vesicle
amoeba
edible
bacterium
Golgi
body
phagocytic
vesicle
lysosome
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