Ion channels as tools to monitor lipid bilayer-membrane protein interactions: gramicidin channels as molecular force transducers

Numerous studies show that membrane protein function depends on the bilayer lipid composition. Specifically, the function of integral membrane proteins varies with lipid bilayer thickness and monolayer equilibrium curvature. In most cases, there is only modest chemical specificity in these membrane lipid-protein interactions.

This lack of chemical specificity, together with the large number of lipid types that are found in the membranes of any given cell, has caused difficulties for attempts to understand the way the function of integral membrane proteins is affected by the bilayer lipid composition. These difficulties arose in part because the results were interpreted within the framework of the Singer-Nicolson fluid mosaic membrane model.

A weakness of the fluid mosaic membrane model was that the lipid bilayer component was assumed to be a passive entity only—that is, a permeability barrier that separated the extracellular and intracellular aqueous phases. The view of the lipid bilayer as a sheet of liquid hydrocarbon led to the notion of bilayer fluidity as an important determinant of protein function.

An important, but neglected consequence of the liquid-crystalline organization of lipid bilayers is that one needs to incorporate the bilayer material properties (thickness and compression modulus, curvature and bending modulus) into a description of membrane protein organization and function. Similarly, one needs to consider specifically the importance of geometric packing criteria for lipid-protein interactions and protein function..