Impact of amylenes in dipeptide-mediated phospholipid vesicle integrity and aggregation

Interactions between lipid membranes are central to biological, biochemical, and biophysical processes. While adhesion between intact vesicles typically requires complex molecular linkers to overcome electrostatic and hydration repulsions, aggregation involves bilayer disruption and loss of vesicle integrity, a phenomenon more often associated with pathology. Here we report a minimal and straightforward route to induce aggregation of zwitterionic vesicles through the combined action of diphenylalanine (Phe-Phe), a dipeptide motif of the Alzheimer's β-amyloid peptide, and amylene, a small apolar alkene used as a chloroform stabilizer. Using NMR spectroscopy, microscopy, and thermodynamic and nanomechanical characterization, we demonstrate that Phe-Phe alone perturbs bilayer organization only mildly, but in the presence of amylene it synergistically drives membrane disruption and vesicle aggregation. These results highlight how the interplay of small molecules can reorganize zwitterionic membranes and eventually induce spontaneous aggregation.