The activity of the amphipathic peptide delta-lysin correlates with phospholipid acyl chain structure and bilayer elastic properties.

Release of lipid vesicle content induced by the amphipathic peptide delta-lysin was investigated as a function of lipid acyl chain length and degree of unsaturation for a series of phosphatidylcholines. Dye efflux and peptide binding were examined for three homologous lipid series: di-monounsaturated, di-polyunsaturated, and asymmetric phosphatidylcholines, with one saturated and one monounsaturated acyl chain. Except for the third series, peptide activity correlated with the first moment of the lateral pressure profile, which is a function of lipid acyl chain structure. In vesicles composed of asymmetric phosphatidylcholines, peptide binding and dye efflux are enhanced compared to symmetric, unsaturated lipids with similar pressure profiles. We attribute this to the entropically more favorable interaction of delta-lysin with partially saturated phospholipids. We find that lipid acyl chain structure has a major impact on the activity of delta-lysin and is likely to be an important factor contributing to the target specificity of amphipathic peptides.