Before the emergence of electron microscopy in the 1950s, scientists did not know the structure of a cell membrane or what its components were; biologists and other researchers used indirect evidence to identify membranes before they could actually be visualized. Specifically, it was through the models of Overton, Langmuir, Gorter and Grendel, and Davson and Danielli, that it was deduced that membranes have lipids, proteins, and a bi-layer. The advent of the electron microscope, the findings of J. David Robertson, the proposal of Singer and Nicolson, and additional work of Unwin and Henderson all contributed to the development of the modern membrane model.
- Gorter and Grendel’s membrane theory (1925)
Evert Gorter and François Grendel (Dutch physiologists) approached the discovery of our present model of the plasma membrane structure as a lipid bi-layer. They simply hypothesized that if the plasma membrane is a bi-layer, then the surface area of the mono-layer of lipids measured would be double the surface area of the plasma membrane. Their experiment supported their hypothesis, which led to the conclusion that cell membranes are composed of two apposing molecular layers.
The two scientists proposed a structure for this bi-layer, with the polar hydrophilic heads facing outwards towards the aqueous environment and the hydrophobic tails facing inwards away from the aqueous surroundings on both sides of the membrane. But they failed to describe the membrane function, and had false assumptions that plasma membranes consist mostly of lipids.
- The Davson and Danielli model with backup from Robertson (1940–1960)
Following the proposal of Gorter and Grendel, doubts inevitably arose over the veracity of having just a simple lipid bi-layer as a membrane. For instance, their model could not provide answers to questions on surface tension, permeability, and the electric resistance of membranes. Therefore, physiologist Hugh Davson and biologist James Danielli suggested that membranes indeed do have proteins. According to them, the existence of these “membrane proteins” explained that which couldn’t be answered by the Gorter-Grendel model.
In 1935, Davson and Danielli proposed that biological membranes are made up of lipid bi-layers that are coated on both sides with thin sheets of protein and they simplified their model into the “pauci-molecular” theory. In short, their model was illustrated as a “sandwich” of protein-lipid-protein. The Davson-Danielli model threw new light on the understanding of cell membranes, by stressing the important role played by proteins in biological membranes.
By the 1950s, cell biologists verified the existence of plasma membranes through the use of electron microscopy. J. David Robertson used this method to propose the unit membrane model. According to the trilaminar pattern of the cellular membrane viewed by Robertson, he suggested that the membranes consist of a lipid bi-layer covered on both surfaces with thin sheets of proteins. This suggestion was a great boost to the proposal of Davson and Danielli.
- Singer and Nicolson’s fluid mosaic model (1972)
In 1972, S. Jonathan Singer and Garth Nicolson developed new ideas for membrane structure. Their proposal was the fluid mosaic model, which is the dominant model now. According to the fluid mosaic model, the plasma membrane is a mosaic of components—primarily, phospholipids, cholesterol, and proteins—that move freely and fluidly in the plane of the membrane. Interestingly enough, this fluidity means that if you insert a very fine needle into a cell, the membrane will simply part to flow around the needle; once the needle is removed, the membrane will flow back together seamlessly.
In general, this model explains most of the criticisms of the Davson–Danielli model. It eliminated the need to accommodate membrane proteins in thin surface layers, proposed that the variability in the protein/lipid ratios of different membranes simply means that different membranes vary in the amount of protein they contain, and showed how the exposure of lipid-head groups at the membrane surface is compatible with their sensitivity to phospholipase digestion. Also, the fluidity of the lipid bi-layers and the intermingling of their components within the membrane make it easy to visualize the mobility of both lipids and proteins.
- Henderson and Unwin’s membrane theory
In their experiment, Unwin and Henderson found that protein extends to both sides of the lipid bi-layer and is composed of seven α-helices packed about 1–1.2 nm apart, 3.5–4.0 nm in length, running perpendicular to the plane of membrane. The molecules are organized around a 3-fold axis with a 2 nm-wide space at the center that is filled with lipids. This elegant work represents the most significant step forward thus far, as it has for the first time provided us with the structure of an integral membrane protein in situ.