Lipid−Peptide Communication in Fluid Bilayers

The influence of channel and nonchannel forms of gramicidin A ( c -gA and nc -gA, respectively) on the mixing behavior of phospholipids derived from 1,2-dimyristoyl- sn -glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE) has been examined in the physiologically relevant fluid phase by means of nearest-neighbor recognition methods (Davidson, S. K. M.; Regen, S. L. Chem. Rev . 1997, 97, 1269). Thus, when disulfide-based dimers were allowed to undergo monomer exchange at 60 °C in the presence of 5 mol % of nc -gA, the molar ratio of heterodimer to each homodimer was 1.55 ± 0.07; replacement of 50% of the exchangeable monomers with 1, 2-dipalmitoyl- sn -glycero-3-phosphocholine (a chemically inert diluent having an intermediate chain length and hydrophobicity) eliminated the ability of nc -gA to induce NNR. In sharp contrast, the presence of c -gA, at concentrations as high as 9 and 17 mol %, left the phospholipids in a randomly arranged state. The ability of gramicidin A to “communicate” its conformation to the surrounding phospholipids implies that lateral transmission of conformational information should also be possible between lipids and proteins in biological membranes.