It isn’t every newsletter issue that FOCUS has the privilege of featuring a scientist whose theory of a fundamental biological phenomenon is accepted throughout the biological and medical sciences as the standard textbook model. Such is the case with S. J. Singer’s and Garth Nicolson’s landmark theory of the Fluid Mosaic Model of cell membranes. This model, proposed in 1972 and published in the prestigious journal SCIENCE, has been called a “unified theory” of the cell membrane. This model has been tested and retested for many decades, and it is now believed to accurately predict the structure and behaviour of all cellular membranes. Over the intervening years this theory has been confirmed by many sophisticated physical and chemical techniques, including one known as freeze-fracture electron microscopy.
The cell membrane is, in the deepest sense, where it’s at—it’s the place where a cell defines itself to other cells and the extracellular environment—where the outside world is separated from an inside world. It is also a dynamic, ever shifting structure where information is exchanged and biological reactions begin and end. The chemistry of life, the exchange and synthesis of molecules, and the transfer of electrons, all occur along and across biological membranes. The cell membrane contains channels and pumps that control the flow of substances and information between cells and it contains highly specific receptors that allow cells to respond to their external milieu and identify and communicate with other cells. It is also the place where nerve impulses are transmitted along nerve cells by changing the electrical potential across the membrane.
When intact and functional, fluid membranes are at the centre of good health; oxidised, damaged membranes leads to pathology and illness. And this is true of both the cell and its outer membrane barrier or cell membrane, and the membrane structures inside the cell, such as in the mitochondria, the little energy powerhouses inside each cell, which are little semi-autonomous organelles on their own. They, too, have membranes that are important as electrical barriers, transport vehicles, and enzyme and communication sites.
The cell membrane was first proposed—as a double layer or bilayer of lipids—in 1925, almost ninety years ago, and it was a revolutionary proposal at the time, but it took several years later to determine where proteins and other components actually fit into this structure. It wasn’t until 1972, with Singer’s and Nicolson’s theory, that the theory came into its own, fully elucidated and able to explain all of the properties of cellular membranes and where each component fit into the structure.
They proposed that:
Membrane components (lipids, glycolipids, proteins, glycoproteins, etc.) are amphipathic in structure—that is, they are asymmetrical in structure, with an outside part that is water-loving and attracts water and an inside part that is water-hating and repels water.
Cellular membranes are constructed as a fluid matrix of two layers or a bilayer of phospholipids along with intercalated proteins and glycoproteins with the water-hating portions of their structures inside the membrane and the water-loving portions facing outside on each side of the membrane.
The membrane takes on an ever-changing or dynamic mosaic form, as if made of “floating spars or buoys” some of which are bound together in complexes and others that are not joined, and have gaps between them along the plane of the membrane. This mosaic of floating spars is made of proteins and glycoproteins that bob and move laterally in the fluid lipid bilayer. In some cases the lipids also get together to form lipid islands that can separate membranes into different fluidity zones. Carbohydrates, mostly on the outer surface of the membrane, are bound to proteins and certain lipids, and function as types of markers of each cell, and this helps cells distinguish one cell from another. They also function as cell barriers and can repel or attract other cells and extracellular matrix that exists between different tissues.
Some of the membrane protein and glycoprotein components are integral to the membrane and fit directly into the lipid bilayer, whereas others are peripheral to the membrane and are attached to one side or the other of the membrane. Some of these peripheral membrane components at the inner surface of the membrane are also attached to other structures inside the cell.
Finally, some of the integral membrane proteins and glycoproteins span the entire lipid bilayer and have portions of their structures on the inner side of the membrane and portions on the outer side of the membrane. These structures, which are often composed of multiple protein and glycoprotein components, are often involved in trans-membrane ion and other molecular transport and also enzymatic functions.
One of the most important discoveries in this model is the dynamic change or motion of the components. Lipids, proteins and complexes of these can move rapidly and laterally within membranes, if they are untethered by other structures associated with the membrane or are not in large multi-component complexes. Fluctuation or motion is the essence of this model. This fluctuation allows maximal responsiveness to the inner and outer (extracellular) environmental changes.
Another key finding of this model is that the two layers of lipids and the proteins and glycoproteins have asymmetrical properties: one part repels water, the other attracts water. This allows the membrane to remain stable yet dynamic and also allow it to form an electrical and ionic barrier. Finally, the model proposes that sugar molecules embedded in the outer layer glycoproteins and some glycolipids partially “mark” and “identify” the cell itself.
Some key phospholipids that compose the lipid bilayer include: phosphatidyl choline (the most prevalent), phosphatidyl serine, phosphatidyl inositol, phosphatidyl ethanolamine and phosphatidyl glycerol (which is the precursor for cardiolipin, a crucial molecule in the inner mitochondrial membrane). In addition to phospholipids, glycolipids and cholesterol are also found in the membrane, and play key roles.
So why, you may wonder, is this dynamic structure of biological membranes so important? Now, with new understanding of the precise composition, location and function of the lipids, proteins and sugars that compose the membrane, we can use dietary methods to provide the essential molecules that rejuvenate and repair biological membranes. This is important, because we have learned that in every disease, illness, and even in normal aging, biological membranes are damaged, and this has important implications in determining whether functions are lost. We can breathe new life into aging and sick cells by understanding and restoring this remarkable invention of nature and evolution.
Disclosure: Garth L. Nicolson, PhD has an educational grant from NTI.