Gramicidin A is a natural antimicrobial peptide produced by Bacillus brevis. Its transmembrane dimer is a cation-selective ion channel. The channel is characterized by the average lifetime of the conducting state and the monomer-dimer equilibrium constant. Dimer formation is accompanied by deformations of the membrane. We theoretically studied how the asymmetry in lipid membrane monolayers influences the formation of the gramicidin A channel. We calculated how the asymmetry in the spontaneous curvature and/or lateral tension of lipid monolayers changes the channel lifetime and shifts the equilibrium constant of the dimerization/dissociation process. For the asymmetry expected to arise in plasma membranes of mammalian cells upon the addition of gramicidin A or its derivatives to the cell exterior, our model predicts a manifold increase in the average lifetime and equilibrium constant.
Keywords: asymmetric lipid membrane; channel lifetime; equilibrium constant; gramicidin A; intrinsic curvature; lateral tension; lipid–protein interaction; membrane biophysics; theory of elasticity.