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

The interaction of biomolecules with cell membranes is crucial due to their important role in governing the 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 present the first evidence that oligomeric intermediates of diphenylalanine exert diverse effects on lipid membranes, influenced by lipid phase and charge. Our findings reveal that the fibrillar morphology of diphenylalanine facilitates the formation of supported phospholipid membranes through liposome deformation. Importantly, metal ion stabilized oligomeric intermediates of diphenylalanine cause wetting, promote vesicle uptake, and induce coalescence, resulting in significant structural alterations of lipid membranes having different charges. These insights open new research directions with profound implications for biomedicine, nanotechnology, and help in fundamental biological understanding.