Cell membranes are “selectively permeable”. This means that they allow the movement of some molecules freely across them, but do not allow the free passage of others.
In broad terms, there are three ways in which molecules move across membranes. This article will consider the processes of diffusion, osmosis and active transport, and consider the clinical relevance of these processes.
Diffusion is the movement of a solute from an area of its high concentration to an area of its low concentration – i.e. down a concentration gradient. This process is “passive” – i.e. it requires no energy; the gradient is enough to drive the process.
Fick’s laws describe diffusion. One simplified arrangement states that ‘the rate of diffusion is proportional to the concentration gradient, the length of the diffusion pathway and the surface area available for diffusion‘. This can be written as follows:
Rate of diffusion ∝ (surface area x concentration gradient)/(length of diffusion pathway)
N.B. Fick’s laws of diffusion are in truth more complex, but beyond the scope of this article.
Diffusion across the cell membrane is either “simple” or “facilitated”. Simple diffusion occurs when molecules can move directly across the membrane without the aid of a carrier protein. Hydrophobic molecules such as O2 and CO2 diffuse readily in this way, as do small uncharged polar molecules such as urea.
However, larger uncharged polar molecules, such as glucose, and charged molecules (ions), need carrier proteins to allow them to cross the lipid bilayer. This process is known as facilitated diffusion. Movement still occurs passively down a concentration gradient; the molecules simply require the help of proteins to aid their passage.
An example of a membrane transport protein involved in facilitated diffusion is the GLUT-2 protein, which is the primary protein involved in the transfer of glucose from the liver into the blood.
Osmosis is the specific term used to describe the diffusion of water molecules from an area of many water molecules to an area of fewer water molecules relative to the mass of solute.
However, it is worth remembering that where there is a high water content, the solution is actually more dilute, so effectively water diffuses from a dilute solution to a more concentrated one, although this is still down a concentration gradient of water molecules.
Water molecules, like urea, are small and uncharged, and thus travel via simple diffusion.
Red blood cells are a key example of the importance of osmosis in the human body. In a hypotonic environment, where there are lots of water molecules outside the cells, water moves into red blood cells, causing them to swell and even to burst. In a hypertonic environment, where there is little water outside the cells, water exits the cells, causing the red blood cells to shrivel.
Thus, maintenance of an isotonic environment in the blood is vital for preserving healthy red blood cells.
Active transport is the movement of molecules from an area of lower concentration to higher concentration, i.e. up a concentration gradient, via specialised membrane proteins. This requires energy, which is provided by the breakdown of ATP. Active transport is a major process; some cells can use up to 50% of their energy on this alone.
A key example of an active transporter is the sodium-potassium (Na/KATP-ase) pump. This exports three sodium ions in return for two potassium ions. This is key to maintaining the resting membrane potential.
It is worth noting that some membrane proteins involved in facilitated diffusion or active transport can carry multiple molecules or ions at once – this is known as “co-transport”. Where the molecules move in the same direction, this is known as “symport”. Where some molecules move one way and others move the other, this is known as “anti-port”. The sodium-potassium pump is an antiporter.
Clinical Relevance – Cystic Fibrosis
The Cystic Fibrosis Transmembrane Conduction Regulator (CFTR) protein is a ligand-gated chloride channel found in the cell membranes of epithelial cells of many organs such as the lungs, pancreas and reproductive tracts.
In healthy people, it usually allows chloride ions to flow freely out of cells. These chloride ions are followed passively by sodium ions, to maintain electrochemical balance, and then water follows via osmosis. This keeps secretions in these organs thin and watery.
In cystic fibrosis, there are various different mutations that lead to either absent or dysfunctional CFTR proteins. This means that chloride ions cannot flow out of cells, and thus neither do sodium or water follow. This results in mucus which is thick and sticky, which is especially problematic in the lungs, pancreas and reproductive tract.
However, note that in the sweat glands, the CFTR protein’s role is slightly different. Rather than allowing chloride ions to flow out of the cells, in sweat glands, the CFTR protein is involved in the reabsorption of chloride, and subsequently sodium, from the sweat. In cystic fibrosis, this cannot occur, and thus sodium and chloride remain in the sweat, giving rise to the classically “salty” sweat seen in CF.