Tuning Liposome Membrane Permeability by Competitive Coiled Coil Heterodimerization and Heterodimer Exchange

Camilla Skyttner, Karin Enander, Christopher Aronsson, Daniel Aili

Membrane active peptides that enable triggered release of liposomal cargo is of large interest for development of liposome-based drug delivery systems but require peptide-lipid membrane interactions that are highly defined and tunable. To this end, we have explored the possibility to use the competing interactions between membrane partitioning and heterodimerization and folding of a set of four different de novo designed coiled coil peptides. Covalent conjugation of the cationic peptides triggered rapid destabilization of membrane integrity and release of encapsulated species. The release was inhibited when introducing complementary peptides as a result of heterodimerization and folding into coiled coils. The degree of inhibition was shown to be dictated by the coiled coil peptide heterodimer dissociation constants, and liposomal release could be reactivated by a heterodimer exchange to render the membrane bound peptide free and thus membrane active. The possibility to tune the permeability of lipid membranes using highly specific peptide folding dependent interactions delineates a new possible approach for further development of responsive liposome-based drug delivery systems.