Composite hydrogels of phenylalanine dipeptides with trivalent metal cations

Abstract

We studied multicomponent hydrogels from a short model peptide, Fmoc-protected diphenylalanine (Fmoc–FF), in the presence of trivalent cations of aluminium (Al) and iron (Fe). Additionally, we investigated the implicit effects of small molecules on the self-assembly of Fmoc–FF by buffering the model system with three commonly used buffers: HEPES, TRIS, and sodium phosphate. The formation and stability of the resulting hydrogels were analyzed through TEM imaging and rheological characterization, and changes in the secondary structure of Fmoc–FF due to addition of metal cations were monitored using ATR-IR spectroscopy. Our results suggest that complexation occurs between the metal cations and the amide groups of the peptide. Furthermore, a spin-probing electron paramagnetic resonance (EPR) strategy, employing persistent nitroxyl radicals TEMPO, TEMPO-benzoate, and Fmoc-TOAC reveals differences in the solvation shell of probes and peptides induced by the presence of metal cations. TEM images revealed different fibrilation mechanisms in the presence of the two cations; while Al-cations lead to formation of water droplets and liquid–liquid phase separation (LLPS), ferric cations form helical superstructures. These differences were then correlated with the toughness of the hydrogels and the distinct types of interactions within them allowing to draw conclusions on the internal nanostructure of these composite materials.