'Detergent-like' permeabilization of anionic lipid vesicles by melittin

Melittin (MLT), the 26-residue toxic peptide from the European honeybee Api s mellifera, is widely used for studying the principles of membrane permeab ilization by antimicrobial and other host-defense peptides. A striking prop erty of MLT is that its ability to permeabilize zwitterionic phospholipid v esicles is dramatically reduced upon the addition of anionic lipids. Becaus e the mechanism of permeabilization may be fundamentally different for the two types of lipids, we examined MLT-induced release of entrapped fluoresce nt dextran markers of two different molecular masses (4 and 50 kDa) from an ionic palmitoyloleoylphosphatidylglycerol (POPG) vesicles. Unlike release f rompalmitoyloleoylphosphatidylcholine (POPC) vesicles, which is highly sele ctive for the 4 kDa marker, implying release through pores of about 25 Angs trom diameter [Ladokhin et al., Biophys. J. 72 (1997) 1762], release from P OPG vesicles was found to be non-selective, i.e., 'detergent-like'. Oriente d circular dichroism measurements of MLT in oriented POPG and POPC multilay ers disclosed that alpha -helical MLT can be induced to adopt a transbilaye r orientation in POPC multilayers, but not in POPG multilayers. The apparen t inhibition of MLT permeabilization by anionic membranes may thus be due t o suppression of translocation ability. (C) 2001 Elsevier Science B.V. All rights reserved.