Revealing the nature of the cell membrane

In the mid-1600s, Robert Hooke, an Englishman, studied thin slices of cork under an early microscope and named the compartments he saw `cells'. Over the next two centuries, biologists found that all types of plants and animals were composed of cells and this lead Matthias Scleiden, Theodor Schwann and Rudolf Virchow to propose successive parts of what is now the foundation of cell theory:

All organisms (plant and animal) are composed of one or more cells
The cell is the basic organizational unit of life
All cells arise from other cells

The third tenet had a `chicken and egg' quality to it which has more recently been addressed by theories of how life began.

1890, Ernst Overton, German physiologist analyzed how substances passed into cell from outside - through the boundary layer. He discovered that non-polar solutes passed though more easily than polar solutes and concluded that boundary layer had dissolving power of a fatty oil. He guessed that it must contain lipids.

1925, E. Gorter and F. Grendel asked two questions:

Does the plasma membrane contain lipid?
If so, how much?

The first question was answered by successful extraction of lipid from red blood cells. By measuring the amount they concluded that there was just enough for the boundary layer to be two molecules thick, i.e. for it to be a lipid bilayer.

The lipid bilayer was shown to be made of phospholipids which have polar (hydrophilic) heads and non-polar (hydrophobic) tails. These phospholipids form bilayer sheets with the polar heads on the outside. It was found that the cell membrane is not simply a lipid bilayer but also contains protein and carbohydrate molecules.

1935, James Danielli and Hugh Davson proposed the Davson-Danielli model which suggested that the protein existed as globular molecules attached to the sides of the lipid bilayer.

In the 1960s, freeze-fracturing (*) and the electron microscope showed that the proteins were actually deeply embedded or penetrating the lipid bilayer.

1972, S. Jonathan Singer and Garth Nicolson proposed a new model, the fluid-mosaic model (sometimes referred to as the Singer-Nicolson model). In addition to knowing that the proteins penetrated the lipid bilayer, they showed that the positions of the proteins were not fixed on the membrane - they move about like a fluid. This was demonstrated by an experiment where cells from humans and mice were fused to form single cells. Initially the proteins from the human and mouse cell are on their respective sides of the fused cell but it was found that after 40 minutes the proteins were distributed evenly over the whole membrane. It has since been found that almost all cells have fluid membranes as proposed by the fluid-mosaic model. In addition to proteins, animal cells contain cholesterol which generally increases the fluidity of the lipid bilayer. However, the mechanism by which this occurs is extremely complex.