Accelerating Lipid Flip-Flop at Low Concentrations: A General Mechanism for Membrane Binding Peptides.

We report a physicochemical investigation of the lipid transport properties of model lipid membranes in the presence of the antimicrobial peptide indolicidin through comparisons of experimental SANS/SAXS scattering techniques to fully atomistic molecular dynamics simulations. In agreement with the experiment, we show that upon peripheral binding of the peptides, even at low concentrations, lipid flip-flop dynamics is greatly accelerated. Computer modeling elucidates the interplay between structural changes and lipid dynamics induced by peptides and proposes a mechanism for the mode of action of antimicrobial peptides, assessing the major role of entropy for the catalysis of the flipping events. The mechanism introduced here is universal for all peptides with preferential peripheral binding to the membrane as it does not depend on the specific amino acid sequence.