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Melittin-membrane interaction follows lipid-specific multi-step mechanism

T.K.H. Nguyen and A. Mechler, School of Molecular Ssciences, La Trobe University, Bundoora, VIC 3086, Australia.

Melittin is considered a typical pore forming antimicrobial peptide. The permeabilization of the membrane has been thoroughly studied and is well described; it is less clear what are the mechanistic steps leading to this final stage. Yet, any membrane specificity, and thus the means of altering thereof, is inherent in the initial stages of the interaction, which is the motivation behind studying the process. Here we report the use of QCM fingerprinting to map out the stages of the membrane disruption mechanism of melittin, using three different model membranes: neat DMPC, DMPC:DMPG (4:1) and DMPC:cholesterol (9:1). We found that the stages of the mechanism are well separated irrespective of the peptide concentration used. The interaction with neat PC and PC:PG model membranes appear to follow similar mechanistic pathways, although there is evidence of material removal at high peptide concentrations for the charged membrane. Addition of cholesterol however considerably alters the interaction mechanism. Thus our results highlight the importance of modeling mammalian membranes with appropriate cholesterol content.