Interaction of elastin-derived peptides with model lipid membranes.

Elastin-derived peptides (EDPs), generated during elastin fragmentation in aging and pathological conditions, are widely recognized for their biological activity through interactions with cell-surface receptors. However, despite their hydrophobic character and proximity to membrane-associated receptors, their capacity to directly interact with lipid bilayers has remained largely unexplored. In this study, we investigated the membrane-binding properties of representative elastin hexa and nonapeptides using a combination of molecular dynamics simulations, potential of mean force calculations, and synchrotron radiation circular dichroism spectroscopy. Our results reveal that the hexapeptide displays minimal membrane interactions while nonapeptides bearing the XGXPGXGXG consensus motif exhibit significant and dynamic membrane association. Cholesterol markedly reduces membrane affinity and membrane interaction stabilizes β-turn conformations, particularly type II turns. Together, these findings demonstrate that certain elastin nonapeptides are capable of direct lipid-bilayer interactions, unveiling a previously underappreciated physicochemical dimension of EDP activity. By providing a receptor-independent route through which EDPs could influence cell behavior wherever they accumulate, this membrane-binding capability may contribute to their biological effects and offers a new perspective on elastin fragmentation in aging and disease.