Scientists had to wait another fifty years for the discovery of the electron microscope, let alone seventy years for the advent of freeze fracturing techniques. Nageli and Cramer in 1855 had already suggested that biological cells are separated from their environment by a membrane possessing special characteristics, and in 1900 Overton performed some simple but classical experiments which proposed that cell membranes were composed of lipids (1). By measuring the permeability of various compounds across the membrane of a frog muscle, Overton found some interesting results. He observed that lipophilic molecules (molecules attracted to fat solvents) could easily cross this cell membrane, however larger lipid insoluble molecules could not.
He also observed that small polar molecules could slowly cross the membrane. Other experiments with the likes of hen eggs suggested the presence of a lipid layer in the membrane. These results became known to biologists across the world and it was generally accepted that a semi-permeable lipid membrane surrounded some if not all cells (2). Although this was opening new doors for cell biologists, the information was widely disregarded.
One hundred years ago biological fact was based on what could be seen and since the proposed lipid membrane was smaller than the wavelength of visible light it could not be studied under the light microscope. Most biologists merely concerned themselves with more evident structures. However, some scientists continued to dedicate their time to examining this invisible structure. Two such biologists were the Dutch Edwin Gorter and F.
Grendel. They recognised in 1925 that two such lipid layers existed. Whilst working on red blood cells they showed the first detailed analysis of structure based on a new model. They extracted the lipid from a red blood cell and spread it as a film on water. The area covered by the lipid turned out to be twice the surface area of the red blood cell. Gorter and Grendel thus concluded that in a cell membrane phospholipids must be arranged as a bilayer, i.
e. two lipid molecules thick (4).