Cell Membrane Physiology

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Cell Membrane Structure and Function
1
Membranes and Cell Transport
• All cells are surrounded
by a plasma membrane.
• Cell membranes are
composed of a lipid
bilayer with globular
proteins embedded in the
bilayer.
• On the external surface,
carbohydrate groups join
with lipids to form
glycolipids, and with
proteins to form
glycoproteins. These
function as cell identity
markers.
2
Fluid Mosaic Model
• In 1972, S. Singer and G. Nicolson proposed the Fluid
Mosaic Model of membrane structure
Glycoprotein
Extracellular fluid
Glycolipid
Carbohydrate
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm
Filaments of
cytoskeleton
3
Phospholipids
•
•
In phospholipids, two of the –OH groups on glycerol are joined
to fatty acids. The third –OH joins to a phosphate group which
joins, in turn, to another polar group of atoms.
The phosphate and polar groups are hydrophilic (polar head)
while the hydrocarbon chains of the 2 fatty acids are
hydrophobic (nonpolar tails).
Choline
Phosphate
Glycerol
Fatty acids
Hydrophilic
head
Hydrophobic
tails
Structural formula
Space-filling model
Phospholipid symbol
4
Phospholipids
• Glycerol
• Two fatty acids
• Phosphate group
Hydrophilic
heads
ECF WATER
Hydrophobic
tails
ICF WATER
5
Phospholipid Bilayer
• Mainly 2 layers of phospholipids; the non-polar tails
point inward and the polar heads are on the surface.
• Contains cholesterol in animal cells.
• Is fluid, allowing proteins to move around within the
bilayer.
Polar
hydro-philic
heads
Nonpolar
hydro-phobic
tails
Polar
hydro-philic
heads
6
The Fluidity of Membranes
•
•
•
•
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.
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.
Lateral movement
(~107 times per second)
Flip-flop
(~ once per month)
7
Membrane Components
•
Steroid Cholesterol
•
•
•
•
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.
Cholesterol
8
Membrane Components
•
Membrane carbohydrates
•
•
•
Interact with the surface molecules of other cells, facilitating cell-cell
recognition
Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell
from another
Membrane Proteins
•
•
•
•
A membrane is a collage of different proteins embedded in the fluid matrix of
the lipid bilayer
Peripheral proteins are appendages loosely bound to the surface of the
membrane
Integral proteins penetrate the hydrophobic core of the lipid bilayer
Many are transmembrane proteins, completely spanning the membrane
Fibers of extracellular
matrix (ECM)
EXTRACELLULAR
SIDE
N-terminus
Glycoprotein
Carbohydrate
Glycolipid
Microfilaments
of cytoskeleton Cholesterol
Peripheral
protein
C-terminus
Integral
protein
a Helix
CYTOPLASMIC
SIDE
9
Functions of Cell Membranes
• Regulate the passage of substance into
and out of cells and between cell
organelles and cytosol
• Detect chemical messengers arriving at
the surface
• Link adjacent cells together by membrane
junctions
• Anchor cells to the extracellular matrix
10
6 Major Functions Of Membrane Proteins
1. Transport. (left) A protein that spans the membrane
may provide a hydrophilic channel across the
membrane that is selective for a particular solute.
(right) Other transport proteins shuttle a substance
from one side to the other by changing shape. Some of
these proteins hydrolyze ATP as an energy ssource to
actively pump substances across the membrane
2. Enzymatic activity. A protein built into the membrane
may be an enzyme with its active site exposed to
substances in the adjacent solution. In some cases,
several enzymes in a membrane are organized as a
team that carries out sequential steps of a metabolic
pathway.
3.
ATP
Enzymes
Signal transduction. A membrane protein may have a
binding site with a specific shape that fits the shape of a
chemical messenger, such as a hormone. The external
messenger (signal) may cause a conformational change
in the protein (receptor) that relays the message to the
inside of the cell.
Signal
Receptor
11
6 Major Functions Of Membrane Proteins
4.
Cell-cell recognition. Some glyco-proteins serve as
identification tags that are specifically recognized
by other cells.
Glycoprotein
5.
Intercellular joining. Membrane proteins of adjacent cells
may hook together in various kinds of junctions, such as
gap junctions or tight junctions
6. Attachment to the cytoskeleton and extracellular matrix
(ECM). Microfilaments or other elements of the
cytoskeleton may be bonded to membrane proteins,
a function that helps maintain cell shape and stabilizes
the location of certain membrane proteins. Proteins that
adhere to the ECM can coordinate extracellular and
intracellular changes
12
Functions of Plasma Membrane Proteins
Outside
Plasma
membrane
Inside
Transporter
Enzyme
Cell surface identity
marker
Cell adhesion
Cell surface
receptor
Attachment to the
cytoskeleton
13
Membrane Transport
• The plasma membrane is the boundary that
separates the living cell from its nonliving
surroundings
• In order to survive, A cell must exchange
materials with its surroundings, a process
controlled by the plasma membrane
• Materials must enter and leave the cell through
the plasma membrane.
• Membrane structure results in selective
permeability, it allows some substances to cross
it more easily than others
14
Membrane Transport
• The plasma membrane exhibits selective
permeability - It allows some substances
to cross it more easily than others
15
Passive Transport
• Passive transport is diffusion of a
substance across a membrane with no
energy investment
• 4 types
• Simple diffusion
• Dialysis
• Osmosis
• Facilitated diffusion
16
Kinetic Theory of Matter
• All atoms and molecules are in constant
random motion. (Energy of motion is
called kinetic energy.)
• The higher the temperature, the faster the
atoms and molecules move.
• We detect this motion as heat.
• All motion theoretically stops at absolute
zero.
17
Solutions and Transport
• Solution – homogeneous mixture of two or
more components
• Solvent – dissolving medium
• Solutes – components in smaller quantities
within a solution
• Intracellular fluid – nucleoplasm and
cytosol
• Extracellular fluid
• Interstitial fluid – fluid on the exterior of the
cell within tissues
• Plasma – fluid component of blood
18
Diffusion
•
•
•
The net movement of a substance from an area of higher
concentration to an area of lower concentration - down a
concentration gradient
Caused by the constant random motion of all atoms and molecules
Movement of individual atoms & molecules is random, but each
substance moves down its own concentration gradient.
Lump
of sugar
Random movement leads to
net movement down a
concentration gradient
Water
No net movement at
equilibrium
19
Diffusion Across a Membrane
•
•
•
The membrane has pores large enough for the molecules to pass
through.
Random movement of the molecules will cause some to pass
through the pores; this will happen more often on the side with more
molecules. The dye diffuses from where it is more concentrated to
where it is less concentrated
This leads to a dynamic equilibrium: The solute molecules continue
to cross the membrane, but at equal rates in both directions.
Net diffusion
Net diffusion
Equilibrium
20
Diffusion Across a Membrane
•
•
•
Two different solutes are separated by a membrane that is
permeable to both
Each solute diffuses down its own concentration gradient.
There will be a net diffusion of the purple molecules toward the left,
even though the total solute concentration was initially greater on
the left side
Net diffusion
Net diffusion
Net diffusion
Net diffusion
Equilibrium
Equilibrium
21
The Permeability of the Lipid Bilayer
• Permeability Factors
• Lipid solubility
• Size
• Charge
• Presence of channels and transporters
• Hydrophobic molecules are lipid soluble and can
pass through the membrane rapidly
• Polar molecules do not cross the membrane
rapidly
• Transport proteins allow passage of hydrophilic
substances across the membrane
22
Passive Transport Processes
• 3 special types of diffusion
that involve movement of
materials across a
semipermeable membrane
• Dialysis/selective diffusion
of solutes
• Lipid-soluble materials
• Small molecules that
can pass through
membrane pores
unassisted
• Facilitated diffusion substances require a
protein carrier for passive
transport
• Osmosis – simple diffusion
of water
23
Osmosis
• Diffusion of the solvent across a
semipermeable membrane.
• In living systems the solvent is
always water, so biologists
generally define osmosis as the
diffusion of water across a
semipermeable membrane:
24
Osmosis
Lower
concentration
of solute (sugar)
Higher
concentration
of sugar
Same concentration
of sugar
Selectively
permeable membrane: sugar molecules cannot pass
through pores, but
water molecules can
Water molecules
cluster around
sugar molecules
More free water
molecules (higher
concentration)
Fewer free water
molecules (lower
concentration)
Osmosis

Water moves from an area of higher
free water concentration to an area
of lower free water concentration
25
Osmotic Pressure
• Osmotic pressure of a solution is the
pressure needed to keep it in equilibrium
with pure H20.
• The higher the concentration of solutes in
a solution, the higher its osmotic pressure.
• Tonicity is the ability of a solution to cause
a cell to gain or lose water – based on the
concentration of solutes
26
Tonicity
• If 2 solutions have equal [solutes], they are called
isotonic
• If one has a higher [solute], and lower [solvent], is
hypertonic
• The one with a lower [solute], and higher [solvent], is
hypotonic
Hypotonic solution
H2O
Lysed
Isotonic solution
Hypertonic solution
H2O
H2O
Normal
H2O
Shriveled
27
Water Balance In Cells With Walls
(b) Plant cell. Plant cells
are turgid (firm) and
generally healthiest in
a hypotonic environment, where the
uptake of water is
eventually balanced
by the elastic wall
pushing back on the
cell.
H2O
Turgid (normal)
H2O
H2O
Flaccid
H2O
Plasmolyzed
28
My definition of Osmosis
• Osmosis is the diffusion of water
across a semi-permeable membrane
from a hypotonic solution to a
hypertonic solution
29
Facilitated Diffusion
•
•
Diffusion of solutes through a semipermeable membrane with the
help of special transport proteins i.e. large polar molecules and ions
that cannot pass through phospholipid bilayer.
Two types of transport proteins can help ions and large polar
molecules diffuse through cell membranes:
Channel proteins – provide a narrow channel for the substance to pass
through.
• Carrier proteins – physically bind to the substance on one side of
membrane and release it on the other.
•
EXTRACELLULAR
FLUID
Channel protein
CYTOPLASM
Solute
Carrier protein
Solute
30
Facilitated Diffusion
• Specific – each channel or carrier
transports certain ions or molecules only
• Passive – direction of net movement is
always down the concentration gradient
• Saturates – once all transport proteins are
in use, rate of diffusion cannot be
increased further
31
Active Transport
• Uses energy (from ATP) to move a
substance against its natural tendency e.g.
up a concentration gradient.
• Requires the use of carrier proteins
(transport proteins that physically bind to
the substance being transported).
• 2 types:
• Membrane pump (protein-mediated active
transport)
• Coupled transport (cotransport).
32
Membrane Pump
• A carrier protein uses energy from ATP to
move a substance across a membrane, up
its concentration gradient:
33
The Sodium-potassium Pump
•
One type of active transport system
[Na+] high
[K+] low
1. Cytoplasmic Na+ binds
to the sodium-potassium
pump.
Na+
Na+
+
NaEXTRACELLULAR
FLUID
[Na+] low
Na+
[K+] high
CYTOPLASM
2. Na+ binding stimulates
phosphorylation by ATP.
Na+
Na+
Na+
Na+
6. K+ is released and Na+
sites are receptive again;
the cycle repeats.
ATP
P
ADP
3. Phosphorylation causes the
protein to change its conformation,
expelling Na+ to the outside.
Na+
K+
P
K+
5. Loss of the phosphate
restores the protein’s
original conformation.
K+
4. Extracellular K+ binds to the
protein, triggering release of the
Phosphate group.
K+
K+
K+
Pi
P
Pi
34
Coupled transport
• 2 stages:
• Carrier protein uses ATP to move a substance across the
membrane against its concentration gradient. Storing energy.
• Coupled transport protein allows the substance to move down its
concentration gradient using the stored energy to move a
second substance up its concentration gradient:
35
Review: Passive And Active Transport Compared
Passive transport. Substances diffuse spontaneously
down their concentration gradients, crossing a
membrane with no expenditure of energy by the cell.
The rate of diffusion can be greatly increased by transport
proteins in the membrane.
Active transport. Some transport proteins act
as pumps, moving substances across a
membrane against their concentration
gradients. Energy for this work is usually
supplied by ATP.
ATP
Diffusion. Hydrophobic
molecules and (at a slow
rate) very small uncharged
polar molecules can diffuse
through the lipid bilayer.
Facilitated diffusion. Many
hydrophilic substances diffuse
through membranes with the
assistance of transport proteins,
either channel or carrier proteins.
36
Bulk Transport
• Allows small particles, or groups of
molecules to enter or leave a cell
without actually passing through the
membrane.
• 2 mechanisms of bulk transport:
endocytosis and exocytosis.
37
Endocytosis
• The plasma membrane envelops small
particles or fluid, then seals on itself to
form a vesicle or vacuole which enters the
cell:
• Phagocytosis
• Pinocytosis
• Receptor-Mediated Endocytosis -
38
Three Types Of Endocytosis
PHAGOCYTOSIS
In phagocytosis, a cell
engulfs a particle by
Wrapping pseudopodia
around it and packaging
it within a membraneenclosed sac large
enough to be classified
as a vacuole. The
particle is digested after
the vacuole fuses with a
lysosome containing
hydrolytic enzymes.
EXTRACELLULAR
FLUID
Pseudopodium
of amoeba
“Food” or
other particle
Bacterium
Food
vacuole
Food vacuole
An amoeba engulfing a bacterium via
phagocytosis (TEM).
PINOCYTOSIS
In pinocytosis, the cell
“gulps” droplets of
extracellular fluid into tiny
vesicles. It is not the fluid
itself that is needed by the
cell, but the molecules
dissolved in the droplet.
Because any and all
included solutes are taken
into the cell, pinocytosis
is nonspecific in the
substances it transports.
1 µm
CYTOPLASM
Pseudopodium
0.5 µm
Plasma
membrane
Pinocytosis vesicles
forming (arrows) in
a cell lining a small
blood vessel (TEM).
Vesicle
39
Process of Phagocytosis
40
Receptor-mediated Endocytosis
Coat protein
Receptor
Receptor-mediated endocytosis
enables the cell to acquire bulk quantities
of specific substances, even though those
substances may not be very concentrated
in the extracellular fluid. Embedded in the
membrane are proteins with specific
receptor sites exposed to the extracellular
fluid. The receptor proteins are usually
already clustered in regions of the
membrane called coated pits, which are
lined on their cytoplasmic side by a fuzzy
layer of coat proteins.
Extracellular substances (ligands) bind
to these receptors. When binding occurs,
the coated pit forms a vesicle containing
the ligand molecules. Notice that there are
relatively more bound molecules (purple)
inside the vesicle, other molecules
(green) are also present. After this
ingested material is liberated from the
vesicle, the receptors are recycled to the
plasma membrane by the same vesicle.
Coated
vesicle
Coated
pit
Ligand
Coat
protein
A coated pit
and a coated
vesicle formed
during
receptormediated
endocytosis
(TEMs).
Plasma
membrane
0.25 µm
41
Exocytosis
• The reverse of endocytosis
• During this process, the membrane of a vesicle
fuses with the plasma membrane and its
contents are released outside the cell:
42
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