History of Cell Membrane Theory - Discovery of Bilayer Structure

Discovery of Bilayer Structure

Thus, by the early twentieth century the chemical, but not the structural nature of the cell membrane was known. Two experiments in 1925 laid the groundwork to fill in this gap. By measuring the capacitance of erythrocyte solutions Fricke determined that the cell membrane was 3.3 nm thick. Although the results of this experiment were accurate, Fricke misinterpreted the data to mean that the cell membrane is a single molecular layer. Because the polar lipid headgroups are fully hydrated, they do not show up in a capacitance measurement meaning that this experiment actually measured the thickness of the hydrocarbon core, not the whole bilayer. Gorter and Grendel approached the problem from a different perspective, performing a solvent extraction of erythrocyte lipids and spreading the resulting material as a monolayer on a Langmuir-Blodgett trough. When they compared the area of the monolayer to the surface area of the cells, they found a ratio of two to one. Later analyses of this experiment showed several problems including an incorrect monolayer pressure, incomplete lipid extraction and a miscalculation of cell surface area. In spite of these issues the fundamental conclusion- that the cell membrane is a lipid bilayer- was correct.

A decade later, Davson and Danielli proposed a modification to this concept. In their model, the lipid bilayer was coated on either side with a layer of globular proteins. According to their view, this protein coat had no particular structure and was simply formed by adsorption from solution. Their theory was also incorrect in that it ascribed the barrier properties of the membrane to electrostatic repulsion from the protein layer rather than the energetic cost of crossing the hydrophobic core. A more direct investigation of the membrane was made possible through the use of electron microscopy in the late 1950s. After staining with heavy metal labels, Sjöstrand et al. noted two thin dark bands separated by a light region, which they incorrectly interpreted as a single molecular layer of protein. A more accurate interpretation was made by J. David Robertson, who determined that the dark electron-dense bands were the headgroups and associated proteins of two apposed lipid monolayers. In this body of work, Robertson put forward the concept of the “unit membrane.” This was the first time the bilayer structure had been universally assigned to all cell membranes as well as organelle membranes.