Peptide-Membrane Interaction Between Targeting And Lysis

Certain cationic peptides interact with biological membranes. These often-complex interactions can result in peptide targeting to the membrane, or in membrane permeation, rupture, and cell lysis. We investigated the relationship between the structural features of membrane active peptides and these effects, to better understand these processes. To this end, we employed a computational method for morphing a membranolytic antimicrobial peptide into a nonmembranolytic mitochondrial targeting peptide by "directed simulated evolution." The results obtained demonstrate that superficially subtle sequence modifications can strongly affect the peptides' membranolytic and membrane-targeting abilities. Spectroscopic and computational analyses suggest that N- and C-terminal structural flexibility plays a crucial role in determining the mode of peptide-membrane interaction.