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

We report a physicochemical investigation of the lipidtransportproperties of model lipid membranes in the presence of the antimicrobialpeptide indolicidin through comparisons of experimental SANS/SAXSscattering techniques to fully atomistic molecular dynamics simulations.In agreement with the experiment, we show that upon peripheral bindingof the peptides, even at low concentrations, lipid flip-flop dynamicsis greatly accelerated. Computer modeling elucidates the interplaybetween structural changes and lipid dynamics induced by peptidesand proposes a mechanism for the mode of action of antimicrobial peptides,assessing the major role of entropy for the catalysis of the flippingevents. The mechanism introduced here is universal for all peptideswith preferential peripheral binding to the membrane as it does notdepend on the specific amino acid sequence.