Influence of pegylation on peptide-mediated liposome fusion

Abstract

The effect of surface-attached PEG on the peptide-mediated fusion of liposomes was investigated. A complementary pair of coiled-coil forming lipidated peptides was introduced to two batches of small unilamellar liposomes separately. Upon mixing, efficient liposome membrane fusion was apparent when the liposomes were not decorated with pegylated lipids, however when the liposomes were pegylated the fusion was inhibited. A FRET-based fluorescence assay indicated that the fusion can be prevented effectively with less than two mole percent of pegylated lipid. DLS and CD spectroscopy were used to further evaluate the influence of pegylation on fusion. These data revealed that the pegylated lipids inhibit peptide complex formation and liposome docking, thereby preventing liposome fusion at the initial stage of the process. In contrast, when the PEG is not covalently attached to the liposome, no fusion inhibition was observed. Thus we conclude that the steric effect of the surface-bound PEG chains, which prevents sustained docking of liposomes, is the main cause of fusion inhibition.