Partitioning of gramicidin A' between coexisting fluid and gel phospholipid phases.

The partitioning behavior of gramicidin A' was investigated in four binary phospholipid mixtures with coexisting fluid and gel phases. The ratio of the equilibrium peptide concentration in the fluid phase to that in the gel phase (i.e., the partition coefficient, Kp) was determined by analysis of the quenching of gramicidin A' tryptophanyl fluorescence by a spin-labeled phosphatidylcholine. The partition coefficient was used as a measure of the relative solubility of gramicidin A' in the four types of gel phases analyzed. The composition of the gel phase was entirely Ca(dioleoylphosphatidylserine)2 (Ca(di18:1-PS)2), or was rich in either distearoylphosphatidylcholine (di18:0-PC), dipalmitoylphosphatidylcholine (di16:0-PC), or dimyristoylphosphatidylcholine (di14:0-PC). Except in the last case, the gel phase was depleted of gramicidin A': Kp approximately 30 when the gel phase was Ca(di18:1-PS)2 or di18:0-PC-rich, Kp approximately 10 when the gel phase was di16:0-PC-rich, and Kp approximately 1 when the gel phase was di14:0-PC-rich. The hydrophobic mismatch between the length of gramicidin A' and the length of the phospholipid acyl chains in the bulk gel phase is greatest with di18:1-PS and di18:0-PC, intermediate with di16:0-PC, and least with di14:0-PC. The Kp measurements presented here are consistent with increasing solubility of gramicidin A' in the gel phase with decreasing hydrophobic mismatch.