LIPID BILAYER ELECTROSTATIC ENERGY, CURVATURE STRESS, AND ASSEMBLY OFGRAMICIDIN CHANNELS

Hydrophobic interactions between lipid bilayers and imbedded membrane proteins couple protein conformation to the mechanical properties of t he bilayer. This coupling is widely assumed to account for the regulat ion of membrane protein function by the membrane lipids' propensity to form nonbilayer phases, which will produce a curvature stress in the bilayer. Nevertheless, there is only limited experimental evidence for an effect of bilayer curvature stress on membrane protein structure. We show that alterations in curvature stress, due to alterations in th e electrostatic energy of dioleoylphosphatidylserine bilayers, modulat e the structurally well-defined gramicidin A monomer <----> dimer reac tion. Maneuvers that decrease the electrostatic energy of the unpertur bed bilayer promote channel dissociation; we measure the change in int eraction energy. The bilayer electrostatic energy thus can affect memb rane protein structure by a mechanism that does not involve the electr ostatic field across the bilayer, but rather electrostatic interaction s among the phospholipid head groups in each monolayer which affect th e bilayer curvature stress. These results provide further evidence for the importance of mechanical interactions between a bilayer and its i mbedded proteins for protein structure and function.