Interaction of Metal Ion Stabilized Oligomeric Dipeptide with Lipid Membrane: Concurrent Observations of Supported Lipid Membrane, Wetting, and Uptake

Abstract

The interaction of biomolecules with cell membranes is crucial due to their important role in governing cellular function and membrane dynamics. However, most of the studies predominantly focus on the interaction of monomeric forms of biomolecules with lipid membranes, leaving the effects of cytotoxic oligomeric self-aggregates largely unexplored. In this study, we report that metal ion stabilized oligomeric intermediates of diphenylalanine cause wetting and uptake, induce coalescence, resulting in significant structural alterations of lipid membranes with varying surface charges. On the other hand, fibrillar morphology of diphenylalanine facilitates the formation of supported phospholipid membranes through liposome deformation. These insights open new research directions with profound implications for biomedicine and nanotechnology and help in fundamental biological understanding. © 2025 American Chemical Society.