The membrane as an environment of minimal interconversion. A circular dichroism study on the solvent dependence of the conformational behavior of gramicidin in diacylphosphatidylcholine model membranes

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Abstract
The conformation of gramicidin in diacylphoshatidylcholine model membranes was investigated as a function of the solvent in which peptide and lipid are initially codissolved. By use of circular dichroism it is demonstrated that, upon removal of the solvent and hydration of the mixed gramicidin/lipid film, it is the conformational behavior of the peptide in the organic solvent that determines its final conformationl in dimyristoylphosphatidylcholine model membranes. As a consequence, parameters that influence the conformation of the peptide in the solvent also play an essential role, such as the gramicidin concentration and the rate of interconversion between different conformations. Of the various solvents investigated, only with trifluoroethanol is it possible directly to incorporate gramicidin entirely in the .beta.6.3-helical (channel) configuration. It is also shown that the conformation of gramicidin in the membrane varies with the peptide/lipid ratio, most likely as a result of intermolecular gramidicin-gramicidin interactions at higher peptide/lipid ratios, and that heat incubation leads to a conformational change in the direction of the .beta.6.3-helical conformation. Using lipids with an acyl chain length varying from 12 carbon atoms in dilauroylphosphatidylcholine to 22 carbon atoms in dierucoylphosphatidylcholine, it was possible to investigate the acyl chain length dependence of the gramicidin conformation in model membranes prepared from these lipids with the use of different solvent systems. It is demonstrated for each solvent system that the distribution between different conformations is relatively independent of the acyl chain length but that the rate at which the conformation converts toward the .beta.6.3-helical configuration upon heating of the samples is affected by the length of the acyl chain. The conversion to the .beta.6.3-helical configuration is fastest in the short-chained dilauroylphosphatidylcholine. Finally, the effect of chemical modification of gramicidin on its conformational behavior was investigated by using the N-terminal-modified derivatives desformylgramicidin and N-acetylprolydesformylgramicidin, the tryptophan-substituted analogue 9-phenylalanylgramicidin, and tryptophan-formylated gramicidin. It is shown that, by codissolving peptide and lipid in trifluoroethanol, all these analogues can be incorporated in the .beta.6.3-helixal conformation but that they differ in their interaction with Na ions, as determined by 23Na NMR measurements.

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