Co-assembly of Peptide Amphiphiles and Lipids into Supramolecular Nanostructures Driven by Anion-π Interactions

Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of peptide amphiphiles and fatty acids driven primarily by anion-pi interactions. The peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion-pi interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR. and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion-pi interactions between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along, the peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the ratio of dodecanoic acid to PA leads to either the formation of large vesicles in the binary systems where the anion-pi interactions are strong, or a heterogeneous mixture of assemblies when the peptide amphiphiles associate weakly with dodecanoic acid. Our findings reveal how co-assembly involving designed specific interactions can drastically change supramolecular morphology and even cross from nano to micro scales.