Flexible Surface Model for Lipid-Protein Interactions

In this chapter, we review the role of membrane elasticity in controlling protein shape and biological function. Conformational changes of membrane proteins potentially involve elastic remodeling of the lipid bilayer. Using a mesoscopic picture, a flexible surface model (FSM) describes the balance of curvature and hydrophobic forces in lipid-protein interactions over large distance scales, explaining influences of bilayer thickness, nonlamellar-forming lipids, and osmotic stress. According to the FSM, the geometrical deformation of the lipids around a protein matches the spontaneous (intrinsic) monolayer curvature, counterbalancing the unfavorable hydrophobic mismatch. As applied to biomembranes, the lipid stress fields govern the energetics of protein conformations due to their different shapes within the bilayer. A significant prototype for this idea is visual rhodopsin, whose conformational energetics are found to be controlled by chemically nonspecific properties of the lipid bilayer. Out-of-plane couplings mediated by curvature strain can be much stronger than the weak interactions in the fluid mosaic model, yielding curvature elastic forces that affect protein shape transitions. Membrane receptors, ion channels, transporters, and membrane-bound peptides can all be affected by the curvature stress field of the lipid bilayer as described by a functional language of shape.