MEMBRANE TRANSPORT 

A. BASIC PRINCIPLES

As the name suggests, the movement of substances across the plasma membrane by passive processes does not require the expenditure of metabolic energy. For this reason, substances that traverse the membrane passively, always do so down their concentration gradient (i.e. from a region where they are at a higher concentration to a region of lower concentration). All passive processes involve the movement of substances by diffusion which refers simply to the tendency for substances to distribute themselves evenly in the environment.

For example, if you add a spoonful of instant coffee to a mug of freshly-boiled water, the molecules in the coffee will very quickly become evenly distributed throughout the water. Diffusion occurs because of the continual random motion of the molecules due to the thermal energy of the system. This motion causes the molecules to collide with each other and ultimately ensures that they become evenly distributed throughout the environment.

There are a number of factors which affect the rate of diffusion and have a bearing on membrane transport:

Molecular Size: Early last century Albert Einstein proposed that the rate of diffusion of a molecule is inversely related to its molecular radius. This proposal was subsequently confirmed and is thought to be a consequence of the fact that small molecules bounce further following a collision with another molecule which means that they diffuse more rapidly than larger molecules.

Distance: Because the driving force for diffusion is the motion of particles and resultant collisions (both of which take a finite time) then the greater the distance the slower the rate of diffusion. This is physiologically important and explains for example why cells are rarely more than 0.2 mm from a blood vessel.

Concentration Gradient: Substances move from a region of high concentration to a region of lower concentration simply because there are more molecules in the region of high concentration which results in a higher frequency of collisions and consequently the progressive migration of molecules into the area of lower concentration until the molecules are evenly distributed.

Plasma Membrane: Of course when we think about diffusion in physiological systems we have to consider that the molecules are moving across a membrane, rather than just within a compartment. We can think of the plasma membrane simply as a barrier to diffusion. Consequently the degree to which a substance can move across the membrane by diffusion depends upon the permeability of the membrane to that particular substance. In addition it should be obvious that the bigger the cell, the larger the area of the plasma membrane available for diffusion and consequently the greater the rate of diffusion.

Taking all of these variables into consideration we can say that for any substance the rate of diffusion (usually designated Q) is given by:

Where: C = Concentration Gradient, P = Permeability, A = Surface Area, MW = Molecular Weight, X = Distance.

As a consequences of this relationship you can see that the rate of diffusion of a substance across the plasma membrane of a cell will be higher when the concentration gradient, permeability of the membrane and the surface area of the membrane are increased and the molecular weight of the substance and diffusing distance are decreased.

Having considered these basic principles of diffusion let us know consider the types of passive process that are utilised in physiological systems as well as the types of substances that are moved by these processes.

B. SIMPLE DIFFUSION

Substances that move across the plasma membrane by simple diffusion do so according to the basic principles alluded to above and importantly without binding to any carrier protein. The two possible pathways for simple diffusion are directly through the lipid bilayer itself or through protein channels. We will consider these two pathways separately:

(i) Simple Diffusion through the Lipid Bilayer
Studies of artificial membranes (either synthetic lipid bilayers or cell membranes with all the proteins removed) have revealed that substances which have a high lipid solubility (such as O₂, CO₂, N₂, alcohols and fatty acids) are able to dissolve in the phospholipids of the lipid bilayer and diffuse directly through the plasma membrane. In general, the higher the lipid solubility of a substance, the faster it will diffuse through the plasma membrane.

(ii) Simple Diffusion through Protein Channels
Small water-soluble substances are repelled by the phospholipids and are unable to cross the lipid bilayer directly. Instead these substances take advantage of the presence of protein channels which traverse the membrane and permit movement by simple diffusion. However because the channels have a relatively small diameter, simple diffusion by this route is largely restricted to small ions such as H⁺, Na⁺, K⁺ and Ca²⁺. An interesting feature of these channels is that they often only permit the movement of one ion species (i.e. are ion selective) and may be gated (i.e. may be open or closed).

C. FACILITATED DIFFUSION

Facilitated diffusion is the mechanism by which most essential metabolic substrates (glucose, some amino acids and soluble vitamins), which are either lipid insoluble or too large to pass through protein channels, traverse the plasma membrane. Although the substance still obeys the basic principles of diffusion outlined above, in facilitated diffusion a carrier protein (blue in the animation opposite) with a specific binding site for the substance assists with the process.  Following binding of the substance to the carrier protein the protein undergoes a conformational change (i.e. it changes shape) which results in the substance being transferred across the membrane. Like simple diffusion of ions through protein channels, the carrier protein is often specific for a particular substance and the substance can move in both directions depending upon the concentration gradient.

However there is one way in which facilitated diffusion differs from simple diffusion and this can be demonstrated by a fairly simple experiment. If you change the concentration of a solute outside a cell and then measure the rate at which it diffuses across the membrane into the cell, then you get two quite different results depending upon whether the solute is moving by simple or facilitated diffusion. If the solute is moving by simple diffusion then there is a fairly linear relationship between solute concentration and rate of diffusion . But if the solute is moving by facilitated diffusion then the rate of diffusion will eventually plateau because once all the carrier proteins are occupied there can be no further increase in the rate of diffusion. This is known as saturation kinetics and is a simple way to distinguish between simple and facilitated diffusion experimentally.

In summary:

• Substances which are lipid-soluble are able to readily diffuse across the plasma membrane by dissolving in the lipid component of the plasma membrane.

• Small water-soluble ions are repelled by the lipid bilayer but are able to diffuse through protein channels which traverse the membrane.

• Substances which are lipid-insoluble or are too large to fit through the protein channels may still diffuse across the membrane providing there is a specific carrier protein to facilitate this process.

One very important consequence of the movement of a large number of physiologically important substances by passive processes is that no cellular energy needs to be expended. This is a very significant economy which allows this cellular energy to be used for other purposes some of which we will consider in the next section.