Functional determinants of a synthetic vesicle fusion system

Selective membrane mergers may be driven by small-molecule recognition between synthetic surface-displayed fusogens which bear vancomycin glycopeptide and its native binding target, D-Ala-D-Ala dipeptide. These recognition motifs are membrane anchored by antimicrobial peptide magainin II and a phosphatidylethanolamine lipid derivative, respectively. We report herein characterization of this synthetic membrane fusion reaction with regard to the following: effects of fusogen concentration, lipid composition, and membrane charge. Our findings indicate that these parameters are determinants of fusion rate, vesicle stability, peptide binding, catalytic fusion and membrane disruption during fusion. Notably, these data indicate the importance of coupling between molecular recognition and insertion for bilayer activation as well as the critical role of membrane subdomain formation for membrane fusion reactivity. These phenomena are general to lipid membrane chemistry, and therefore these findings provide a guideline for understanding more complex biomembrane systems.