Membrane-active
peptides that enable the triggered release of liposomal
cargo are of great interest for the 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 the 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 the 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 the further development of responsive
liposome-based drug delivery systems