Chapter 7 Membrane Structure and Function
Lecture Outline
Overview: Life at the Edge
·
The
plasma membrane separates the living cell from its nonliving surroundings.
·
This
thin barrier, 8 nm thick, controls traffic into and out of the cell.
·
Like
all biological membranes, the plasma membrane is selectively permeable, allowing some substances to cross more
easily than others.
Concept 7.1 Cellular membranes are fluid mosaics of lipids and
proteins
·
The
main macromolecules in membranes are lipids and proteins, but carbohydrates are
also important.
·
The
most abundant lipids are phospholipids.
·
Phospholipids
and most other membrane constituents are amphipathic
molecules.
°
Amphipathic
molecules have both hydrophobic regions and hydrophilic regions.
·
The
arrangement of phospholipids and proteins in biological membranes is described
by the fluid mosaic model.
Membrane models have evolved to fit new data.
·
Models
of membranes were developed long before membranes were first seen with electron
microscopes in the 1950s.
°
In
1915, membranes isolated from red blood cells were chemically analyzed and
found to be composed of lipids and proteins.
°
In
1925, E. Gorter and F. Grendel reasoned that cell membranes must be a
phospholipid bilayer two molecules thick.
°
The
molecules in the bilayer are arranged such that the hydrophobic fatty acid
tails are sheltered from water while the hydrophilic phosphate groups interact
with water.
°
Actual
membranes adhere more strongly to water than do artificial membranes composed
only of phospholipids.
°
One
suggestion was that proteins on the surface of the membrane increased adhesion.
°
In
1935, H. Davson and J. Danielli proposed a sandwich model in which the
phospholipid bilayer lies between two layers of globular proteins.
°
Early
images from electron microscopes seemed to support the Davson-Danielli model,
and until the 1960s, it was widely accepted as the structure of the plasma
membrane and internal membranes.
°
Further
investigation revealed two problems.
§
First,
not all membranes were alike. Membranes differ in thickness, appearance when
stained, and percentage of proteins.
à
Membranes
with different functions differ in chemical composition and structure.
§
Second,
measurements showed that membrane proteins are not very soluble in water.
§
Membrane
proteins are amphipathic, with hydrophobic and hydrophilic regions.
§
If
membrane proteins were at the membrane surface, their hydrophobic regions would
be in contact with water.
·
In
1972, S. J. Singer and G. Nicolson presented a revised model that proposed that
the membrane proteins are dispersed and individually inserted into the
phospholipid bilayer.
°
In
this fluid mosaic model, the hydrophilic regions of proteins and phospholipids
are in maximum contact with water, and the hydrophobic regions are in a
nonaqueous environment within the membrane.
·
A
specialized preparation technique, freeze-fracture, splits a membrane along the
middle of the phospholipid bilayer.
·
When
a freeze-fracture preparation is viewed with an electron microscope, protein
particles are interspersed in a smooth matrix, supporting the fluid mosaic
model.
Membranes are fluid.
·
Membrane
molecules are held in place by relatively weak hydrophobic interactions.
·
Most
of the lipids and some proteins drift laterally in the plane of the membrane,
but rarely flip-flop from one phospholipid layer to the other.
·
The
lateral movements of phospholipids are rapid, about 2 microns per second. A
phospholipid can travel the length of a typical bacterial cell in 1 second.
·
Many
larger membrane proteins drift within the phospholipid bilayer, although they
move more slowly than the phospholipids.
°
Some
proteins move in a very directed manner, perhaps guided or driven by motor
proteins attached to the cytoskeleton.
°
Other
proteins never move and are anchored to the cytoskeleton.
·
Membrane
fluidity is influenced by temperature. As temperatures cool, membranes switch
from a fluid state to a solid state as the phospholipids pack more closely.
·
Membrane
fluidity is also influenced by its components. Membranes rich in unsaturated
fatty acids are more fluid that those dominated by saturated fatty acids
because the kinks in the unsaturated fatty acid tails at the locations of the
double bonds prevent tight packing.
·
The
steroid cholesterol is wedged between phospholipid molecules in the plasma membrane
of animal cells.
·
At
warm temperatures (such as 37°C), cholesterol restrains the movement of
phospholipids and reduces fluidity.
·
At
cool temperatures, it maintains fluidity by preventing tight packing.
·
Thus,
cholesterol acts as a “temperature buffer” for the membrane, resisting changes
in membrane fluidity as temperature changes.
·
To
work properly with active enzymes and appropriate permeability, membranes must
be about as fluid as salad oil.
·
Cells
can alter the lipid composition of membranes to compensate for changes in
fluidity caused by changing temperatures.
°
For
example, cold-adapted organisms such as winter wheat increase the percentage of
unsaturated phospholipids in their membranes in the autumn.
°
This
prevents membranes from solidifying during winter.
Membranes are mosaics of structure and
function.
·
A
membrane is a collage of different proteins embedded in the fluid matrix of the
lipid bilayer.
·
Proteins
determine most of the membrane’s specific functions.
·
The
plasma membrane and the membranes of the various organelles each have unique
collections of proteins.
·
There
are two major populations of membrane proteins.
°
Peripheral proteins are not embedded in the
lipid bilayer at all.
§
Instead,
they are loosely bound to the surface of the protein, often connected to
integral proteins.
°
Integral proteins penetrate the hydrophobic
core of the lipid bilayer, often completely spanning the membrane (as transmembrane proteins).
§
The
hydrophobic regions embedded in the membrane’s core consist of stretches of
nonpolar amino acids, often coiled into alpha helices.
§
Where
integral proteins are in contact with the aqueous environment, they have
hydrophilic regions of amino acids.
°
On
the cytoplasmic side of the membrane, some membrane proteins connect to the
cytoskeleton.
°
On
the exterior side of the membrane, some membrane proteins attach to the fibers
of the extracellular matrix.
·
The
proteins of the plasma membrane have six major functions:
1. Transport of specific
solutes into or out of cells.
2. Enzymatic activity,
sometimes catalyzing one of a number of steps of a metabolic pathway.
3. Signal transduction,
relaying hormonal messages to the cell.
4. Cell-cell recognition,
allowing other proteins to attach two adjacent cells together.
5. Intercellular joining of
adjacent cells with gap or tight junctions.
6. Attachment to the cytoskeleton and extracellular matrix, maintaining cell shape
and stabilizing the location of certain membrane proteins.
Membrane carbohydrates are important for
cell-cell recognition.
·
The
plasma membrane plays the key role in cell-cell recognition.
°
Cell-cell
recognition, the ability of a cell to distinguish one type of neighboring cell
from another, is crucial to the functioning of an organism.
°
This
attribute is important in the sorting and organization of cells into tissues
and organs during development.
°
It
is also the basis for rejection of foreign cells by the immune system.
°
Cells
recognize other cells by binding to surface molecules, often carbohydrates, on
the plasma membrane.
·
Membrane
carbohydrates are usually branched oligosaccharides with fewer than 15 sugar
units.
·
They
may be covalently bonded to lipids, forming glycolipids, or more commonly to
proteins, forming glycoproteins.
·
The
oligosaccharides on the external side of the plasma membrane vary from species
to species, from individual to individual, and even from cell type to cell type
within the same individual.
°
This
variation distinguishes each cell type.
°
The
four human blood groups (A, B, AB, and O) differ in the external carbohydrates
on red blood cells.
Membranes have distinctive inside and outside
faces.
·
Membranes
have distinct inside and outside faces. The two layers may differ in lipid
composition. Each protein in the membrane has a directional orientation in the
membrane.
·
The
asymmetrical orientation of proteins, lipids and associated carbohydrates
begins during the synthesis of membrane in the ER and Golgi apparatus.
·
Membrane
lipids and proteins are synthesized in the endoplasmic reticulum. Carbohydrates
are added to proteins in the ER, and the resulting glycoproteins are further
modified in the Golgi apparatus. Glycolipids are also produced in the Golgi
apparatus.
·
When
a vesicle fuses with the plasma membrane, the outside layer of the vesicle
becomes continuous with the inside layer of the plasma membrane. In that way,
molecules that originate on the inside face of the ER end up on the outside
face of the plasma membrane.
Concept 7.2 Membrane structure results in
selective permeability
·
A
steady traffic of small molecules and ions moves across the plasma membrane in
both directions.
°
For
example, sugars, amino acids, and other nutrients enter a muscle cell, and
metabolic waste products leave.
°
The
cell absorbs oxygen and expels carbon dioxide.
°
It
also regulates concentrations of inorganic ions, such as Na+, K+,
Ca2+, and Cl−, by shuttling them across the
membrane.
·
However,
substances do not move across the barrier indiscriminately; membranes are
selectively permeable.
·
The
plasma membrane allows the cell to take up many varieties of small molecules
and ions and exclude others. Substances that move through the membrane do so at
different rates.
·
Movement
of a molecule through a membrane depends on the interaction of the molecule
with the hydrophobic core of the membrane.
°
Hydrophobic
molecules, such as hydrocarbons, CO2, and O2, can
dissolve in the lipid bilayer and cross easily.
°
The
hydrophobic core of the membrane impedes the direct passage of ions and polar
molecules, which cross the membrane with difficulty.
§
This
includes small molecules, such as water, and larger molecules, such as glucose
and other sugars.
§
An
ion, whether a charged atom or molecule, and its surrounding shell of water
also has difficulty penetrating the hydrophobic core.
·
Proteins
assist and regulate the transport of ions and polar molecules.
·
Specific
ions and polar molecules can cross the lipid bilayer by passing through transport proteins that span the
membrane.
°
Some
transport proteins, called channel
proteins, have a hydrophilic channel that certain molecules or ions can use
as a tunnel through the membrane.
°
For
example, the passage of water through the membrane can be greatly facilitated
by channel proteins known as aquaporins.
°
Other
transport proteins, called carrier
proteins, bind to molecules and change shape to shuttle them across the membrane.
·
Each transport protein is specific
as to the substances that it will translocate.
°
For
example, the glucose transport protein in the liver will carry glucose into the
cell but will not transport fructose, its structural isomer.
Concept 7.3 Passive transport is diffusion of a
substance across a membrane with no energy investment
·
Diffusion is the tendency of
molecules of any substance to spread out in the available space.
°
Diffusion
is driven by the intrinsic kinetic energy (thermal motion or heat) of molecules.
·
Movements
of individual molecules are random.
·
However,
movement of a population of molecules may be directional.
·
Imagine
a permeable membrane separating a solution with dye molecules from pure water.
If the membrane has microscopic pores that are large enough, dye molecules will
cross the barrier randomly.
·
The
net movement of dye molecules across the membrane will continue until both
sides have equal concentrations of the dye.
·
At
this dynamic equilibrium, as many molecules cross one way as cross in the other
direction.
·
In
the absence of other forces, a substance will diffuse from where it is more
concentrated to where it is less concentrated, down its concentration gradient.
·
No
work must be done to move substances down the concentration gradient.
·
Diffusion
is a spontaneous process that decreases free energy and increases entropy by
creating a randomized mixture.
·
Each
substance diffuses down its own
concentration gradient, independent of the concentration gradients of other
substances.
·
The
diffusion of a substance across a biological membrane is passive transport because it requires no energy from the cell to
make it happen.
°
The
concentration gradient itself represents potential energy and drives diffusion.
·
Because
membranes are selectively permeable, the interactions of the molecules with the
membrane play a role in the diffusion rate.
·
Diffusion
of molecules of limited permeability through the lipid bilayer may be assisted
by transport proteins.
Osmosis is the passive transport of water.
·
Differences
in the relative concentration of dissolved materials in two solutions can lead
to the movement of ions from one to the other.
°
The
solution with the higher concentration of solutes is hypertonic relative to the other solution.
°
The
solution with the lower concentration of solutes is hypotonic relative to the other solution.
°
These
are comparative terms.
§
Tap
water is hypertonic compared to distilled water but hypotonic compared to
seawater.
°
Solutions
with equal solute concentrations are isotonic.
·
Imagine
that two sugar solutions differing in concentration are separated by a membrane
that will allow water through, but not sugar.
·
The
hypertonic solution has a lower water concentration than the hypotonic
solution.
°
More
of the water molecules in the hypertonic solution are bound up in hydration
shells around the sugar molecules, leaving fewer unbound water molecules.
·
Unbound
water molecules will move from the hypotonic solution, where they are abundant,
to the hypertonic solution, where they are rarer. Net movement of water
continues until the solutions are isotonic.
·
The
diffusion of water across a selectively permeable membrane is called osmosis.
·
The
direction of osmosis is determined only by a difference in total solute concentration.
°
The
kinds of solutes in the solutions do
not matter.
°
This
makes sense because the total solute concentration is an indicator of the
abundance of bound water molecules (and, therefore, of free water molecules).
·
When
two solutions are isotonic, water molecules move at equal rates from one to the
other, with no net osmosis.
·
The
movement of water by osmosis is crucial to living organisms.
Cell survival depends on balancing water
uptake and loss.
·
An animal
cell (or other cell without a cell wall) immersed in an isotonic environment
experiences no net movement of water across its plasma membrane.
°
Water
molecules move across the membrane but at the same rate in both directions.
°
The
volume of the cell is stable.
·
The
same cell in a hypertonic environment will lose water, shrivel, and probably
die.
·
A
cell in a hypotonic solution will gain water, swell, and burst.
·
For
organisms living in an isotonic environment (for example, many marine
invertebrates), osmosis is not a problem.
°
The
cells of most land animals are bathed in extracellular fluid that is isotonic
to the cells.
·
Organisms
without rigid walls have osmotic problems in either a hypertonic or hypotonic
environment and must have adaptations for osmoregulation,
the control of water balance, to maintain their internal environment.
·
For
example, Paramecium, a protist, is
hypertonic to the pond water in which it lives.
°
In
spite of a cell membrane that is less permeable to water than other cells,
water still continually enters the Paramecium
cell.
°
To
solve this problem, Paramecium cells
have a specialized organelle, the contractile vacuole, which functions as a
bilge pump to force water out of the cell.
·
The
cells of plants, prokaryotes, fungi, and some protists have walls that
contribute to the cell’s water balance.
·
A
plant cell in a hypotonic solution will swell until the elastic cell wall
opposes further uptake.
°
At
this point the cell is turgid (very
firm), a healthy state for most plant cells.
·
Turgid
cells contribute to the mechanical support of the plant.
·
If
a plant cell and its surroundings are isotonic, there is no movement of water
into the cell. The cell becomes flaccid
(limp), and the plant may wilt.
·
The
cell wall provides no advantages when a plant cell is immersed in a hypertonic
solution. As the plant cell loses water, its volume shrinks. Eventually, the
plasma membrane pulls away from the wall. This plasmolysis is usually lethal.
Specific proteins facilitate passive transport
of water and selected solutes.
·
Many
polar molecules and ions that are normally impeded by the lipid bilayer of the
membrane diffuse passively with the help of transport proteins that span the
membrane.
·
The
passive movement of molecules down their concentration gradient via transport
proteins is called facilitated
diffusion.
·
Two
types of transport proteins facilitate the movement of molecules or ions across
membranes: channel proteins and carrier proteins.
·
Some
channel proteins simply provide hydrophilic corridors for the passage of
specific molecules or ions.
°
For
example, water channel proteins, aquaporins,
greatly facilitate the diffusion of water.
·
Many ion channels function as gated channels. These channels open or
close depending on the presence or absence of a chemical or physical stimulus.
°
If
chemical, the stimulus is a substance other than the one to be transported.
§
For
example, stimulation of a receiving neuron by specific neurotransmitters opens
gated channels to allow sodium ions into the cell.
§
When
the neurotransmitters are not present, the channels are closed.
·
Some
transport proteins do not provide channels but appear to actually translocate
the solute-binding site and solute across the membrane as the transport protein
changes shape.
°
These
shape changes may be triggered by the binding and release of the transported
molecule.
·
In
certain inherited diseases, specific transport systems may be defective or
absent.
°
Cystinuria
is a human disease characterized by the absence of a protein that transports
cysteine and other amino acids across the membranes of kidney cells.
°
An
individual with cystinuria develops painful kidney stones as amino acids
accumulate and crystallize in the kidneys.
Concept 7.4 Active transport uses energy to move
solutes against their gradients
·
Some
transport proteins can move solutes across membranes against their
concentration gradient, from the side where they are less concentrated to the
side where they are more concentrated.
·
This
active transport requires the cell
to expend metabolic energy.
·
Active
transport enables a cell to maintain its internal concentrations of small
molecules that would otherwise diffuse across the membrane.
·
Active
transport is performed by specific proteins embedded in the membranes.
·
ATP
supplies the energy for most active transport.
°
ATP
can power active transport by transferring a phosphate group from ATP (forming
ADP) to the transport protein.
°
This
may induce a conformational change in the transport protein, translocating the
solute across the membrane.
·
The
sodium-potassium pump actively
maintains the gradient of sodium ions (Na+) and potassium ions (K+)
across the plasma membrane of animal cells.
°
Typically,
K+ concentration is low outside an animal cell and high inside the
cell, while Na+ concentration is high outside an animal cell and low
inside the cell.
°
The
sodium-potassium pump maintains these concentration gradients, using the energy
of one ATP to pump three Na+ out and two K+ in.
Some ion pumps generate voltage across
membranes.
·
All
cells maintain a voltage across their plasma membranes.
·
Voltage
is electrical potential energy due to the separation of opposite charges.
°
The
cytoplasm of a cell is negative in charge compared to the extracellular fluid
because of an unequal distribution of cations and anions on opposite sides of
the membrane.
°
The
voltage across a membrane is called a membrane
potential, and ranges from −50 to −200 millivolts (mV). The
inside of the cell is negative compared to the outside.
·
The
membrane potential acts like a battery.
·
The
membrane potential favors the passive transport of cations into the cell and
anions out of the cell.
·
Two
combined forces, collectively called the electrochemical
gradient, drive the diffusion of ions across a membrane.
°
One
is a chemical force based on an ion’s concentration gradient.
°
The
other is an electrical force based on the effect of the membrane potential on
the ion’s movement.
·
An
ion does not simply diffuse down its concentration gradient but diffuses down
its electrochemical gradient.
°
For
example, there is a higher concentration of Na+ outside a resting
nerve cell than inside.
°
When
the neuron is stimulated, a gated channel opens and Na+ diffuse into
the cell down their electrochemical gradient. The diffusion of Na+
is driven by their concentration gradient and by the attraction of cations to
the negative side of the membrane.
·
Special
transport proteins, electrogenic pumps,
generate the voltage gradient across a membrane.
°
The
sodium-potassium pump in animals restores the electrochemical gradient not only
by the active transport of Na+ and K+, setting up a
concentration gradient, but because it pumps two K+ inside for every
three Na+ that it moves out, setting up a voltage across the
membrane.
·
The
sodium-potassium pump is the major electrogenic pump of animal cells.
·
In
plants, bacteria, and fungi, a proton
pump is the major electrogenic pump, actively transporting H+
out of the cell.
·
Proton
pumps in the cristae of mitochondria and the thylakoids of chloroplasts
concentrate H+ behind membranes.
·
These
electrogenic pumps store energy that can be accessed for cellular work.
In cotransport, a membrane protein couples the
transport of two solutes.
·
A
single ATP-powered pump that transports one solute can indirectly drive the
active transport of several other solutes in a mechanism called cotransport.
·
As
the solute that has been actively transported diffuses back passively through a
transport protein, its movement can be coupled with the active transport of
another substance against its concentration gradient.
·
Plants
commonly use the gradient of hydrogen ions generated by proton pumps to drive
the active transport of amino acids, sugars, and other nutrients into the cell.
·
One
specific transport protein couples the diffusion of protons out of the cell and
the transport of sucrose into the cell. Plants use the mechanism of
sucrose-proton cotransport to load sucrose into specialized cells in the veins
of leaves for distribution to nonphotosynthetic organs such as roots.
Concept 7.5 Bulk transport across the plasma
membrane occurs by exocytosis and endocytosis
·
Small
molecules and water enter or leave the cell through the lipid bilayer or by
transport proteins.
·
Large
molecules, such as polysaccharides and proteins, cross the membrane via
vesicles.
·
During
exocytosis, a transport vesicle
budded from the Golgi apparatus is moved by the cytoskeleton to the plasma
membrane.
·
When
the two membranes come in contact, the bilayers fuse and spill the contents to
the outside.
·
Many
secretory cells use exocytosis to export their products.
·
During
endocytosis, a cell brings in
macromolecules and particulate matter by forming new vesicles from the plasma
membrane.
·
Endocytosis
is a reversal of exocytosis, although different proteins are involved in the
two processes.
°
A
small area of the plasma membrane sinks inward to form a pocket.
°
As
the pocket deepens, it pinches in to form a vesicle containing the material
that had been outside the cell.
·
There
are three types of endocytosis: phagocytosis (“cellular eating”), pinocytosis
(“cellular drinking”), and receptor-mediated endocytosis.
·
In
phagocytosis, the cell engulfs a
particle by extending pseudopodia around it and packaging it in a large
vacuole.
·
The
contents of the vacuole are digested when the vacuole fuses with a lysosome.
·
In
pinocytosis, a cell creates a
vesicle around a droplet of extracellular fluid. All included solutes are taken
into the cell in this nonspecific process.
·
Receptor-mediated
endocytosis
allows greater specificity, transporting only certain substances.
·
This
process is triggered when extracellular substances, or ligands, bind to special receptors on the membrane surface. The
receptor proteins are clustered in regions of the membrane called coated pits,
which are lined on their cytoplasmic side by a layer of coat proteins.
·
Binding
of ligands to receptors triggers the formation of a vesicle by the coated pit,
bringing the bound substances into the cell.
·
Receptor-mediated
endocytosis enables a cell to acquire bulk quantities of specific materials
that may be in low concentrations in the environment.
°
Human
cells use this process to take in cholesterol for use in the synthesis of
membranes and as a precursor for the synthesis of steroids.
°
Cholesterol
travels in the blood in low-density lipoproteins (LDL), complexes of protein
and lipid.
°
These
lipoproteins act as ligands to bind to LDL receptors and enter the cell by
endocytosis.
°
In
an inherited disease called familial hypercholesterolemia, the LDL receptors
are defective, leading to an accumulation of LDL and cholesterol in the blood.
°
This
contributes to early atherosclerosis.