Membrane Transport
Cell membranes
• The cell membrane or plasma membrane is
a biological membrane that separates the
interior of all cells from the outside
environment.
• They are not passive barriers. They control the
structures and environments of the
compartments they define, and thereby the
metabolism of these compartments. The
membrane itself is a metabolic compartment
with unique functions.
Membrane functions
• surrounds the cytoplasm of a cell and physically
separates the intracellular components from the
extracellular environment
• anchors the cytoskeleton (a cellular 'skeleton' made
of protein and contained in the cytoplasm) and
gives shape to the cell
• attachs the cell to the extracellular matrix and other
cells to help group cells together to form tissues
• provides mechanisms for cell-to-cell
communication
• is differentially permeable and regulates what
enters and exits the cell, thus facilitating the
transport of materials needed for survival
• maintains the cell potential
Structural organisation of cell membrane
• The membrane consists of a lipid bi-layer. Phopholipids, the
main lipid component, are oriented in such way that the
hydrophobic non-polar tails are pointing towards each others
while the hydrophylic polar phosphate heads point toward the
cytosolic (internal) and external surface. This creates an
hydrophobic barrier around the cell.
Phopholipid
• Phospholipids are composed of two aliphatic chains
and contain a phosphate group on the head
Fluid mosaic model
•
Other components of the membrane are other lipids (e.g. cholesterol, glycolipids) and
proteins.
Body Solutions
• Intra cellular fluid (ICF)‐ within cells
• Extra cellular Fluid (ECF)‐ outside cells
Inter cellular = tissue fluid = interstitial fluid
Plasma = fluid portion of blood
• Composition of fluids change as substances
move between compartments
nutrients, oxygen, ions and wastes move in both
directions across capillary walls and cell
membrane
Relative permeability of a phospholipid
bilayer to various substances
Type of substance
Examples
Behaviour
Gases
CO2, N2, O2
Permeable
Small uncharged
polar molecules
Urea, water, ethanol
Permeable, totally or
partially
Large uncharged
polar molecules
glucose, fructose
Not permeable
Ions
K+, Na+, Cl-, HCO3-
Not permeable
Charged polar
molecules
ATP, amino acids,
glucose-6-phosphate
Not permeable
Selective Permeability of Membrane
• Lipid bilayer
 permeable to nonpolar, uncharged molecules oxygen, CO2, steroids
 permeable to water which flows through gaps that
form in hydrophobic core of membrane as
phospholipids move about
• Transmembrane proteins act as specific channels:
 small and medium polar & charged particles
• Macromolecules unable to pass through themembrane
 vesicular transport
Gradients Across the Plasma Membrane
• Membrane can maintain difference in concentration of a
substance inside versus outside of the membrane
(concentration gradient)
more O2 & Na+ outside of cell membrane
more CO2 and K+ inside of cell membrane
• Membrane can maintain a difference in charged ions
between inside & outside of membrane (electrical
gradient or membrane potential)
• Substances always move down their concentration
gradient and towards the oppositely charged area
ions have electrochemical gradients
Membrane Transport
• Passive transport mechanisms requires no ATP
random molecular motion of particles provides
the necessary energy
filtration, diffusion, osmosis
• Active transport mechanisms consumes ATP
active transport and vesicular transport
Thermodynamics
• A physiological process can only take place if it
complies with basic thermodynamic principles.
A general principle of thermodynamics that governs
the transfer of substances through membranes is that
the exchange of free energy, ΔG, for the transport of
a mole of a substance of concentration C1 in a
compartment to another compartment where it is
C2
present at C2
G  RT ln
C1
• C2 is less than C1 ΔG is negative, and the process is
thermodynamically favorable.
Chemical potential
Electrochemical potential
U
k 
 k
G
k 
 k
S ,V , l  k  const
T , P, l  k  const
  0  RT ln C
~
  0  RT ln C  ZF
Passive transport
• Teorell equation describes the motion of chemical
species in a fluid medium
d~
j  UC

dx
j

where
S t
j is the "diffusion flux" (amount of substance per unit
area per unit time), U is mobility of particles, C is the
concentration
• Nernst–Planck equation describes the flux of ions
under the influence of both an ionic concentration
gradient and an electric field
dC
d
j  URT
 UCZF
dx
dx
where
Simple Diffusion
• Simple Diffusion – the net movement of particles
from area of high concentration to area of low
concentration (Down gradient) due to their
constant, spontaneous motion.
Fick's law
dC
j  URT
dx
where
D is the diffusion coefficient
D  URT
dC
j  D
dx
Diffusion Rates
Factors affecting diffusion rate through a membrane
• temperature ‐ ↑ temp., ↑ motion of particles
• molecular weight ‐ larger molecules move slower
• steepness of concentrated gradient ‐ ↑ difference, ↑
rate
• membrane surface area ‐ ↑ area, ↑ rate
• membrane permeability ‐ ↑ permeability, ↑ rate
Facilitated diffusion
• It also called carrier-mediated diffusion, is the
movement of molecules across the cell
membrane via special transport proteins that are
embedded within the cellular membrane. Many
large molecules, such as glucose, are insoluble
in lipids and too large to fit through the
membrane pores. Therefore, it will bind with its
specific carrier proteins, and the complex will
then be bonded to a receptor site and moved
through the cellular membrane.
Facilitated diffusion
• transport of solute through a membrane down its
concentration gradient
• Does not consume ATP
• Solute attaches to binding site on carrier, carrier
changes confirmation, then releases solute on other
side of membrane
• Saturation occurs in
facilitated diffusion
because not enough
carriers may be
available to handle all
the free solute
molecules.
The rate of movement
may reach a
maximum.
Membrane Carriers
• Uniport carries only one solute at a time
• Symport carries 2 or more solutes
simultaneously in same direction
(cotransport)
• Antiport carries 2 or more solutes in
opposite directions (countertransport)
sodium‐potassium pump brings in K+ and
removes Na+ from cell
• Carriers employ two methods of transport
facilitated diffusion
active transport
Osmosis
• If two solutions of
different concentration
are separated by a semipermeable membrane
which is permeable to to
the smaller solvent
molecules but not to the
larger solute molecules,
then the solvent will tend
to diffuse across the
membrane from the less
concentrated to the more
concentrated solution.
This process is called
osmosis.
Osmosis
• Osmosis ‐ flow of water from one side of a
selectively permeable membrane to the other
from side with higher water concentration to the
side with lower water concentration
• reversible attraction of water to solute
• particles forms hydration spheres
•
makes those water molecules less
• available to diffuse back to the side
• from which they came
•
Aquaporins ‐ channel proteins
• specialized for passage of water
Filtration
• is movement of water and solute molecules across the
cell membrane due to hydrostatic pressure generated
by the cardiovascular system. Depending on the size
of the membrane pores, only solutes of a certain size
may pass through it. For example, the membrane
pores of the Bowman's capsule in the kidneys are
very small, and only albumins, the smallest of the
proteins, have any chance of being filtered through.
On the other hand, the membrane pores of liver cells
are extremely large, to allow a variety of solutes to
pass through and be metabolized.
Active Transport
• Active transport – carrier‐mediated transport
of solute through a membrane up (against)
its concentration gradient
• ATP energy consumed to change carrier
• Examples of uses:
• sodium‐potassium pump keeps K+
concentration higher inside the cell
bring amino acids into cell
pump Ca2+ out of cell
Primary and secondary active transport
• Active transport is the movement of a
substance against its concentration gradient
(from low to high concentration). In all cells,
this is usually concerned with accumulating
high concentrations of molecules that the cell
needs, such as ions, glucose and amino acids.
If the process uses chemical energy, such as
from adenosine triphosphate (ATP), it is
termed primary active transport. Secondary
active transport involves the use of an
electrochemical gradient.
Primary active transport
• It also called direct active transport, directly uses energy
to transport molecules across a membrane.
• Most of the enzymes that perform this type of transport
are transmembrane ATPases. A primary ATPase
universal to all life is the sodium-potassium pump, which
helps to maintain the cell potential.
Secondary active transport
• In co-transport, energy is used to transport
molecules across a membrane; however, in contrast to
primary active transport, there is no direct coupling of
ATP; instead, the electrochemical potential difference
created by pumping ions out of the cell is used.
• The two main forms of this are antiport and symport.
Mechanism
• The pump, with good binds ATP, binds 3 intracellular
Na+ ions.
• ATP is hydrolyzed, leading to phosphorylation of the
pump at a highly conserved aspartate residue and
subsequent release of ADP.
• A conformational change in the pump exposes the Na+
ions to the outside. The phosphorylated form of the pump
has a low affinity for Na+ ions, so they are released.
• The pump binds 2 extracellular K+ ions. This causes the
dephosphorylation of the pump, reverting it to its
previous conformational state, transporting the K+ ions
into the cell.
• The unphosphorylated form of the pump has a higher
affinity for Na+ ions than K+ ions, so the two bound K+
ions are released. ATP binds, and the process starts again.
Sodium‐Potassium Pump
• Each pump cycle consumes one ATP and exchanges
three Na+ for two K+
• Keeps the K+ concentration higher and the Na+
concentration lower with in the cell than in ECF
• Necessary because Na+ and K+ constantly leak
through membrane
half of daily calories utilized for Na+ ‐ K+ pump
Ion concentration gradient
Functions of Na+ ‐K+ Pump
• Regulation of cell volume
 “fixed anions” attract cations causing osmosis
 cell swelling stimulates the Na+‐ K+ pump to ↓ ion concentration, ↓
osmolarity and cell swelling
• Secondary active transport
 steep concentration gradient maintained between one side of the
membrane and the other – (water behind a dam)
 Sodium‐glucose transport protein (SGLT) – simultaneously binds Na+
and glucose and carries both into the cell
 does not consume ATP
• Heat production
 thyroid hormone increase # of Na+ ‐ K+ pumps
 consume ATP and produce heat as a by‐product
• Maintenance of a membrane potential in all cells
 pump keeps inside more negative, outside more positive
 necessary for nerve and muscle function
Vesicular Transport
• Vesicular Transport – processes that move large particles, fluid
droplets, or numerous molecules at once through the membrane in
vesicles – bubblelike enclosures of membrane
 motor proteins consumes ATP
• Endocytosis –vesicular processes that bring material into the cell
phagocytosis – “cell eating” ‐ engulfing large particles
pseudopods phagosomes macrophages
pinocytosis – “cell drinking” taking in droplets of ECF containing
molecules useful in the cell
pinocytic vesicle
receptor‐mediated endocytosis – particles bind to specific receptors on
plasma membrane
clathrin‐coated vesicle
• Exocytosis – discharging material from the cell
• Utilizes motor proteins energized by ATP