Finite-concentration thermodynamics of amphipathic peptide adsorption on curved lipid membranes.

Curvature plays a central role in regulating peptide and protein adsorption on lipid membranes. Using a molecular-theory framework in a semi-open ensemble, we quantify how membrane curvature, ionic strength, membrane surface charge, and lipid packing jointly modulate peptide adsorption. We focus on LL-37, a human antimicrobial peptide sensitive to membrane curvature. We show that curvature sensing arises from collective effects: although local peptide-membrane free-energy profiles are only weakly curvature-dependent, the overall amount of adsorbed peptide increases markedly on curved geometries due to redistribution of peptide populations between distinct adsorption modes, corresponding to peptides lying parallel or standing upright on the membrane surface. Environmental variables modulate the magnitude of peptide adsorption: reduced ionic strength amplifies curvature sensitivity, membrane neutralization lowers adsorption while preserving binding, and loosening lipid packing enhances adsorption. These results establish a molecular-level thermodynamic framework for curvature-dependent peptide adsorption beyond the single-molecule limit.