The unexpected players: alkene-dipeptide bridges as mediators of vesicle adhesion

Abstract

Adhesion of lipid membranes is ubiquitous in many biological, biochemical and biophysical processes. It requires the membranes of apposing bilayers to be in very close proximity, overcoming electrostatic and hydration repulsion forces. Adhesion of lipid vesicles is an essential early step for fusion and involves the action of proteins leading to lipid mixing. When no content mixing between vesicles occurs, adhesion can lead to aggregation, a useful phenomenon to form assemblies with interest in tissue mimics and functional biomaterials. However, it is not a straightforward process and it typically relies on vesicle functionalization by the use of complex linkers. In this work we report a very straightforward approach to induce aggregation in zwitterionic vesicles. We show the synergistic action of diphenylalanine, a small dipeptide, with amylene, an alkene customarily used as chloroform stabilizer, in inducing adhesion and aggregation of zwitterionic lipid vesicles. A combination of NMR spectroscopy, microscopy and thermodynamic characterization techniques is used to yield a detailed picture of the mechanisms by which the interplay between these small molecules affects bilayer organization, stability and adhesion.