MEMBRANE

PERMIABILITY AND
TRANSPORT
DONNA MAE I. ILAR
BS BIOLOGY 3A
• Cells are the main units of organization in biology. All cells are contained by a cell
membrane (biomembrane) selectively open to some chemicals and ions but acts as a
barrier to undesired components.
• To put it another way, biomembranes are enclosing membranes which function
as selectively permeable barriers to chemicals and ions. It should be noted though that
the title biomembrane may denote a wide range of definitions; especially, cellular
membranes should not be confused with isolating tissues formed by layers of cells
(e.g., mucous membranes). Here the focus would be on biological membranes in the
form of cell membranes, often consist of a phospholipid bilayer with embedded,
integral, and/or peripheral proteins responsible for communication and transportation of
chemicals and ions.
• When a membrane separates two aqueous compartments, some chemicals can
move across the membrane while others cannot. This behavior can be seen with
pure synthetic phospholipid membranes, which are practically biomembranes with
no protein. Membrane proteins play a crucial role as transporters in expediting the
ions and chemical transfers across the cell membranes. Based on the transport
mechanism and permeability, solutes can be divided into three main groups as
follows.

1. Small lipophilic (lipid soluble) molecules that transfer through the membrane by
the sole diffusion.
2. Molecules that cross the membrane with the aid of protein channels.
3. Very large molecules that do not cross the membrane at all.
• Schematic cartoon given by can clearly illustrate the selective
permeability of biomembranes for different solutes. A few lipophilic
substances move freely across the cell membrane by passive diffusion.
Lipophilicity is a measure for the tendency of a compound to partition into
nonpolar (organic) solvent (versus aqueous solvent). Most small
molecules/ions need the assistance of specific protein channels to
transport them through the cell membrane. These inside-out protein
channels are called transporters. Finally, the very large molecules do not
cross the membrane, except in certain special cases.

Selective permeability of biomembrane

Generally speaking, two different classes of membrane transports can be
considered:
• Rapid, stereo-selective protein-mediated transport
• Slow, non-specific diffusion of molecules across cell membrane
• It is worth noting that the mediated transport can be used in drug delivery and
defects in transport are the causes of many diseases.
• Small Lipophilic Molecules (Passive Diffusion)
• Certain substances easily pass through the membrane by passive diffusion.
Examples of chemicals that passively diffuse across the cell membranes are gases,
like O2 and CO2, and small relatively hydrophobic molecules, such as fatty acids and
alcohols. Logarithm of octanol/water partition coefficient of the solute ( Ko/w) can be
a measure of lipophilicity (higher the log( Ko/w), higher the lipophilicity of the solute
will be). However, larger lipophilicity values should not be always interpreted as
better passive diffusion. The underlying reason is that there are two counter-effect
parameters: besides being lipid-soluble (to cross the membrane), the solute should
also possess enough water solubility to dissolve in the body fluids. Usually, a
compound with log(Ko/w) > 5 is too hydrophobic to passively diffuse through the
biological membranes.
• In contrast to small lipophilic molecules, in absence of protein channels, it is difficult
for water to pass through the pure phospholipid membranes via diffusion. Moreover,
almost all polar and charged molecules such as sugars, amino acids, and ions
completely fail to cross the pure phospholipid membranes.
• Polar and Charged Molecules (Protein-Mediated Transfer)
• Biological membranes are permeable not only to gases and small lipophilic
molecules (by passive diffusion processes), but also to many polar and charged
molecules, including water, but through a different path. There are many
different proteins located in biomembranes with the main function of effectively
transporting certain solutes across the membrane. According to their functions,
there are two main groups of transport proteins: channel proteins and carrier
proteins. Channel proteins promote the transfer of water molecules and certain
ions by forming hydrophilic pores, while carrier proteins bind to specific solutes
and carry them across the membrane [2]. All in all, whether it is of channel or
carrier type, protein functions as an enzyme expediting the transfer of polar
and charged molecules. All channel proteins and some carrier proteins facilitate
the transfer of chemical/ions downhill respected to the concentration gradient,
a process known as facilitated diffusion. Facilitated diffusion requires no energy
input, in contrast to active transport processes (solute transport against the
concentration gradient) that require an external source energy.
• Large Molecules (Membrane Barriers)
• Very large molecules like proteins, polysaccharides or nucleic acids, do not diffuse across the cell
membranes at all. They can pass through the membrane only when broken down into their
component monomers (e.g., amino acids, sugars, or nucleotides).
• Passive and Active Transport
• Most biologically important solutes require protein carriers to cross cell membranes, by a process
of either passive or active transport. Active transport requires the cell to expend energy to move
the materials, while passive transport can be done without using cellular energy. To put it another
way, active transport uses energy to move a solute "uphill" against its gradient, whereas in
facilitated diffusion, a solute moves down its concentration gradient and no energy input is
required.
• Therefore, to summarize, transport of solutes across cell membranes by protein carriers can occur
in one of two ways [2]:
• Downhill movement of solutes from regions of higher to lower concentration level, with the
assistance of the protein carrier to pass through the membrane. This process is called passive
transport or facilitated diffusion, and does not require energy.
• Uphill movement of solute against the concentration gradient driving force (from regions of lower
to higher concentration). Based on the chemical driving force, this process is unfavorable and
requires some form of chemical energy to occur (active transport).
• The type of transport process, facilitated/active transport, a biological cell employs is
strictly dependent on its specific needs and concentration level of chemical/ions. For
example, red blood cells use facilitated diffusion to transfer glucose across
membranes, whereas intestinal epithelial cells rely on active transport to take in
glucose from the gut [2]. Facilitated diffusion is effective for red blood cells primarily
because the glucose concentration in the blood is stable and higher than the cellular
level. In contrast, active transport is needed for the gut since there are large
fluctuations of glucose level as a result of eating.
• encapsulates different transfer mechanisms discussed so far. Please note that the
concentration gradient driving force is assumed downward in this schematic diagram.
• Facilitated Diffusion
• In principle, there are two types of facilitated diffusion carriers as follows:
1. Water molecules or certain ions can be transported by channel proteins. By forming a
protein-lined pathway across the membrane, proteins can appreciably speed up the
transfer rate of such solutes. It should be noted though that each type of channel
protein is very selective to a specific ion/chemical. For example, some channels allow
only K+ ions to pass whereas they act like a barrier to other ions. Moreover, many of
these channels are gated. To simply explain the issue, consider that the pathways are
closed and unavailable for transport unless specific signals are given. One of the most
vital functions of gated channels is in regulating nerve conduction in animals.
2. Organic molecules, like sugars and amino acids, can be transferred across the
membrane via uniporters which carry molecules along the concentration gradient.
Almost all tissues in any living being have a variety of uniporters for transfer of glucose
and amino acids into their cells.
• Active Transport
• Active transporters make an endergonic reaction (K eq < 1) more exergonic (K eq > 1) by
coupling the first reaction to a second highly exergonic reaction (e.g., ATP-hyrolysis)
through common intermediates to change the direction of transport (e.g., Na export
from low to high concentration). To be more precise, when a transfer is not
electrochemically favorable, another source of energy (which can come from another
reaction) is required to force the transfer. These can be accomplished by a direct result
of ATP hydrolysis (ATP pump) or by coupling the movement of one substance with that
of another (symport or antiport). Active transport may use energy to transport solutes
into or out of the cell, but always in opposite direction of the electrochemical driving
force.
• As mentioned before, biomembranes separate the intracellular and extracellular
environments that are different in many aspects such as concentration levels of ions
and chemicals. For example, in human tissues, all cells have a higher concentration
level of sodium ion outside the cell than inside, while the exact opposite condition is
maintained for the potassium ion ( Cinside > Coutside). Regarding charged solutes and ions,
besides the concentration gradient, the electrical voltage can come to play too; there is
an electrical driving force for cations and anions to move along and opposite the
electric field, respectively.
• This rule can show how an endergonic reaction (K eq < 1) can shift to the RHS (producing more
product) by being coupled to another highly exergonic reaction (K eq >> 1) through a common
intermediate [3]. To clarify the issue let us consider the active transport of the sodium ion as
follows:
• Reaction 1: Ion Transport
• The ion transport equation can be written as

ΔG=RTln Co/Ci + zFV

• which for Na+ gives the Gibbs free energy of 2.98 kcal/mol, or equivalently, an equilibrium constant
of 0.0065. In this equation, R is the universal gas constant (1.987 cal/(mol.K)), T is absolute
temperature (K), F is the Faraday's constant (23060 cal/(volt.mol)) and z is the the valence (charge
number) of the ion. Moreover, subscripts i and o denote the inside and outside of the cell.
• Reaction 2: ATP Hydrolysis
• As mentioned before, the required excess energy for active transport can come from ATP
hydrolysis. Typical Gibbs free energy change for ATP hydrolysis is around -13 kcal/mol, making the
total Gibbs free energy change of 2.98 - 13 = -10.02 kcal/mol. Therefore, the overall reaction is
highly shifted to produce more product by being coupled with the strictly exothermic ATP hydrolysis
reaction.
• Osmosis: Water Permeability
• Osmosis (transfer of water molecules through the bilayer) is a function of the relative
concentration levels of solute molecules in intracellular and extracellular environments.
Water molecules can readily pass through special protein channels. If the total
concentration of all dissolved solute is unbalanced ( Cinside ~= Coutside), there would be a
net water flow into or out of the biological cell. the direction and magnitude of the
water flow is strictly dependent on whether the cell’s environment is isotonic,
hypotonic, or hypertonic which are illustrative measures for the relative concentrations
of solutes inside and outside the cell.
• Isotonic Solutions (Cinside = Coutside)
• in isotonic case, the total molar concentration of dissolved solutes is the same for the
intracellular and extracellular environments. In this condition, the inward and outward
flows of water molecules are exactly balanced. the net flow of water is zero and total
number of water molecules (or equivalently water concentration, Cw) is remained
constant on each side. A 0.9% solution of sodium hydroxide is a perfect example of
isotonic solution to animal cells. During experiments, like exposing membranes to
different solutions, it is highly recommended to use an isotonic solution to prevent
osmotic effects (e.g., swelling and shrinking of the cell) which can seriously damage
the biological cells.
• Hypotonic Solutions (Cinside > Coutside)
• In a hypotonic condition, molar concentration of the total dissolved solutes is
higher inside the cell than that in the extracellular environment. Obviously, low
concentration of solutes in an aqueous solution can be interpreted as high
concentration of water. Therefore, it is straightforward to see if Cinside >
Coutside → Cw, inside < Cw, outside, providing a driving force for a net inward water flow to
the cell. Hence, when a cell is exposed to such hypotonic conditions, there is net
water movement into the cell and passing time, the concentration of water
molecules inside the cell would be increased. Because of this considerable
accumulation of water molecules, cells will swell and may even burst if the excess
accumulated water is not removed from the intracellular environment.
• Hypertonic Solutions (Cinside < Coutside)
• Cell behavior under hypertonic condition is exactly the opposite of what
explained for the hypotonic case ( Cinside < Coutside → Cw, inside > Cw, outside). In this
case, the water concentration is higher in cell's interior than in its outside, so
there would be a net outward water flow from the cell. Therefore, passing time,
the water concentration level will decrease inside the cell and cell will shrink. As
an important consequence of the low water level, the ability of cell to function or
divide would be gradually lost. It is interesting that hypertonic solutions like
concentrated syrups have been used since ancient times for food preservation.
This can be explained through the fact that microbial cells that would cause
spoilage are dehydrated in these very hypertonic environments and would be
unable to function
• Transport Disorders
• Considering the remarkable specificity of the transporters, it is not surprising that
sometimes there are defects in transport systems. Nowadays, several different
diseases known to be due to transport defects. In many of the cell membrane
diseases, proteins do not transport materials properly. Some of the membrane
transport disease are hereditary. An archetypical example of such transport diseases
is Cystinuria, an inherited autosomal recessive disease that is characterized by
abnormally high amino acid (cystine) concentration level in the urine, that may result
in the formation of cystine stones in the kidneys. Another example can be 
Cystic Fibrosis (CF) which is caused by a mutation in the cystic fibrosis
transmembrane conductance regulator, CFTR, a protein that helps move salt and
water across the membrane. It is a genetic disorder that affects mostly the lungs but
also the pancreas, liver, kidneys, and intestine. Long-term issues include breathing
problems and coughing up mucus as a result of frequent lung infections. In a patient
with CF, the cells do not secrete enough water; when it happens in the lungs, it
causes the mucus to become extremely thick.
• Driving Forces
• The permeability of a membrane can be defined as the passive diffusion rate of
permeated molecules across the biomembrane. It is unanimously accepted that
permeability of any specific molecule depends mainly on charge number, polarity, size,
and to some extent, to the molar mass of the molecule. It should be noted though that
both the nature of the bilayer and the prevalent environments can play a significant
role too. As mentioned before, because of the inevitable hydrophobic nature of the
biomembranes, small uncharged molecules pass across the membrane more easily than
charged, large ones.
• Permeability Model
• Schematic diagram of diffusion through a bilayer is sketched in which two aqueous
solutions S1 and S2 are separated by the biomembrane. Superscripts "aq" and "m"
denote solute concentrations at bulk aqueous solutions and surfaces of the
membrane, respectively. As it can be seen, the concentration gradient is
considered to be from S1 to S2, providing the chemical driving force of the
transport. To mathematically describe the permeability, let us first introduce the
useful concept of partition coefficient. At thermodynamic equilibrium, the equality
of the chemical potentials of solute j in two different intracellular and extracellular
phases can be expressed as.
• μ j /I + RT ln C j/i = μ j/o + RT ln C j/o
• Then, the partition coefficient can be defined as

• Ki/o = Cj/i Cj/o = exp⎛⎝⎜−(μji−μjo)RT⎞⎠⎟

Schematic diagram of mass transfer through bilayer

• References
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2. PearsonPractice Hall - Lab Simulations.
www.schenectady.k12.ny.us/putman/biology/data/biomembrane1/intro.html
3. W. D. Stein. Transport and Diffusion across Cell Membranes. Academic Press, 1986.
4. Selectively Permeable Membranes. Study.com: 
http://study.com/academy/lesson/selectively-permeable-membranes-definition-examples-qu
iz.html
5. R. Fettiplace & D. A. Haydon. Water Permeability of Lipid Membranes. Physiological
Reviews 1980 (60) 510 - 550.
6. Cell Membrane. Wikipedia: https://en.Wikipedia.org/wiki/Cell_membrane#Permeability
7. Nernst Equation. Wikipedia: https://en.Wikipedia.org/wiki/Nernst_equation