Design of a short membrane-destabilizing peptide covalently bound to liposomes

We characterized the physical and biological properties of a 14-residue amphipathic sequence called SFP (for short fusogenic peptide). At acidic pH, this short synthetic peptide interacts with various phospholipidic monolayers. These interactions were correlated with a pH-dependent conformational transition of SFP resulting in a hydrophobic alpha-helical structure. The hemolysis assay showed a pH-dependent weak membrane destabilizing activity of SFP. However, membrane anchoring of SFP through a covalently bound myristic acid enhanced by 1000-fold its membrane-destabilizing power. Moreover, SFP covalently bound to fluorescent-labeled liposomes induced a pH-dependent mixing of both membranes. SFP, a small synthetic peptide, is thus able to mimick many aspects of viral protein-induced membrane fusion: conformational change, membrane destabilization, membrane anchoring and finally pH-dependent lipid mixing.