The most drastic mode of membrane disruption caused by a-helical antimicrobial peptides involves membrane lysis wherein the membrane is broken down into small, multimolecular aggregates composed of the amphiphilic peptide and lipid molecules. The structural constitutions of amphiphilicity of the peptide and the lipid are however markedly different. The a-helical peptides are facial amphiphiles with one surface being hydrophobic and the other being hydrophilic.  In contrast, phospholipids have a conventional head-tail amphiphilic structure with a hydrophilic head group and hydrophobic tail group. As a result the peptides and the lipids in their pure states are expected to self-assemble into very different aggregate morphologies. In this study, we examine how these two molecules of dissimilar amphiphilicity will assemble together to form mixed aggregates.  We consider three different structural arrangements influenced by the  preferred natural curvature of phospholipids being lamellar: a bicelle (small bilayer) made of lipids with peptides coating the exposed hydrophobic surface of the lipids; a bicelle of lipids with a toroidal rim populated by both lipids and peptides; and a mixed globular micelle incorporating both lipids and peptides. We examine based on free energy considerations which of these three structures is favored for the mixed aggregates as a function of the molecular characteristics of the peptide and the lipid and also the peptide to lipid ratio.

Peptide induced membrane lysis: How are the peptides and phospholipids organized in the mixed aggregates?

239th National Meeting (2010)

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