Concentration Effects in Peptide–Lipid Bilayer Interactions: A Coarse-Grained Molecular Dynamics Study

In this work, we explore the assumption and predictions of a two-state model by Huang and collaborators that was developed to quantify peptide-induced pore formations in lipid bilayers. Specifically, we report on Martini 2 and Martini 3 molecular dynamics simulations of melittin, a bee venom-derived peptide with antimicrobial properties, and an amyloid peptide fragment Aβ(29–42) interacting with a POPC bilayer. We focus on the effects of peptide concentration on the cooperative peptide–lipid bilayer interactions. We found that peptides first adsorb at the membrane interface and then, beyond a critical peptide-to-lipid ratio, insert into the membrane to form transmembrane clusters. However, in contrast to Huang’s model, this cooperative effect does not coincide with a turnover in the rate of membrane thinning. This difference may stem from the peptide concentration dependence of the bilayer mechanical properties that is not accounted for in Huang’s model. We also found that antimicrobial melittin and amyloidogenic Aβ(29–42) show similar characteristics of peptide–lipid interaction. This supports the conjecture that antimicrobial peptides and amyloidogenic peptides may use the same molecular mechanism to disrupt lipid membranes.