High efficiency liposome fusion induced by reducing undesired membrane peptides interaction

Abstract

AbstractA full membrane fusion model which attains both complete lipid mixing and content mixing liposomal membranes mediated by coiled-coil forming lipopeptides LPK [L-PEG12-(KIAALKE)3] and LPE [L-PEG12-(EIAALEK)3] is presented. The electrostatic effects of lipid anchored peptides on fusion efficiency was investigated. For this, the original amino acid sequence of the membrane bound LPK was varied at its ‘f’-position of the helical structure, i.e. via mutating the anionic glutamate residues by either neutral serines or cationic lysines. Both CD and fluorescence measurements showed that replacing the negatively charged glutamate did not significantly alter the peptide ability to form a coiled coil, but lipid mixing and content mixing assays showed more efficient liposome-liposome fusion resulting in almost quantitative content mixing for the lysine mutated analogue (LPKK) in conjunction with LPE. A mechanism is proposed for a fusion model triggered by membrane destabilizing effects mediated by the membrane destabilizing activety of LPK in cooperation with the electrostatic activity of LPE. This new insight may enlightens the further development of a promising nano carrier tool for biomedical applications.