RELEASE OF LIPID VESICLE CONTENTS BY AN ANTIBACTERIAL CECROPIN A-MELITTIN HYBRID PEPTIDE

A synthetic cecropin A(1-8)-melittin(1-18) hybrid peptide, with antima larial and antibacterial properties, promotes leakage of aqueous conte nts of phospholipid vesicles, as determined by measuring the induced r elease of vesicle-entrapped fluorescence probes. The release of vesicl e contents corresponds to an all-or-none mechanism. High molecular wei ght entrapped solutes (fluorescence-labeled dextrans, 20 and 4 kDa mol ecular mass) are also released by the peptide. This fact and the high peptide stoichiometry required for the release of vesicle contents sug gest a detergent-like disruption of the bilayer. The leakage process i s not related to any membrane event requiring lipid-mixing between bil ayers. The peptide destabilizes both negatively and neutrally charged phospholipid vesicles. The thermal variation of the fluorescence aniso tropy of 1,6-diphenyl-1,3,5-hexatriene-labeled vesicles is modified by the peptide. Circular dichroism and tryptophan fluorescence emission spectra reveal conformational changes in the peptide molecule upon int eraction with the lipid vesicles. These changes are consistent with an increased cr-helical content and a less polar environment for the sin gle tryptophan residue of the peptide. The leakage induced in phosphat idylserine vesicles is a faster process than in phosphatidylcholine ve sicles, while the peptide is more effective in releasing the contents of the latter type of vesicles. This suggests that acidic phospholipid s may modulate the effect of the peptide on membranes.