Regulation of membrane protein function by lipid bilayer elasticity—a singlemolecule technology to measure the bilayer properties experienced by an embeddedprotein

Abstract

Membrane protein function is generally regulated by the molecular composition of the hostlipid bilayer. The underlying mechanisms have long remained enigmatic. Some cases involvespecific molecular interactions, but very often lipids and other amphiphiles, which areadsorbed to lipid bilayers, regulate a number of structurally unrelated proteins in anapparently non-specific manner. It is well known that changes in the physical properties ofa lipid bilayer (e.g., thickness or monolayer spontaneous curvature) can affect thefunction of an embedded protein. However, the role of such changes, in the generalregulation of membrane protein function, is unclear. This is to a large extentdue to lack of a generally accepted framework in which to understand the manyobservations. The present review summarizes studies which have demonstrated that thehydrophobic interactions between a membrane protein and the host lipid bilayerprovide an energetic coupling, whereby protein function can be regulated by thebilayer elasticity. The feasibility of this ‘hydrophobic coupling mechanism’ has beendemonstrated using the gramicidin channel, a model membrane protein, in planar lipidbilayers. Using voltage-dependent sodium channels, N-type calcium channels andGABAA receptors, it has been shown that membrane protein function in living cells can beregulated by amphiphile induced changes in bilayer elasticity. Using the gramicidin channelas a molecular force transducer, a nanotechnology to measure the elastic propertiesexperienced by an embedded protein has been developed. A theoretical and technologicalframework, to study the regulation of membrane protein function by lipid bilayer elasticity,has been established.