Fine tuning the morphology of peptide amphiphile nanostructures via co-assembly

The self-assembly of peptide amphiphiles (PAs) in aqueous solution yields nanoconstructs displaying a rich spectrum of sizes and morphologies, including micelles, fibers, and lamellar ribbons. The morphology impacts the bioactivity of the PAs and, thus, efforts have been made to control it by tuning their molecular structure or the solution pH. However, synthesizing new PAs is time consuming and biomedical applications limit the pH to physiologically relevant ranges. This work demonstrates that the composition of a binary mixture of co-assembled PAs serves as a powerful approach to exert rational control over the morphology, size and transition pHs of the supramolecular nanostructures. We combined light scattering, SAXS, TEM and AFM experiments and theoretical predictions using a Molecular Theory (MOLT) to construct composition-pH morphology diagrams for three relevant PA mixtures. For C₁₆KK/C₁₆KKK mixtures (C₁₆: palmitoyl and K: lysine), we demonstrate fine tuning of the micelle-to-fiber transition pH by varying the composition of the system. For a mixture of oppositely charged PAs, C₁₆EEE/C₁₆KKK (E: glutamic acid), theory and experiments reveal interesting composition-driven micelle-to-fiber-to-micelle transitions. The C₁₆KK/C₁₆EE mixture exhibits three different morphologies-micelles, fibers, and lamellae-and regions of the morphology diagram showing coexistence between fibers and lamellae. MOLT calculations also provide insights into the internal organization of the assemblies and predict that the nanostructure radius can also be tuned by the composition of the mixture, in agreement with SAXS observations.