The Introduction of a Cysteine Residue Modulates The Mechanical Properties of Aromatic‐Based Solid Aggregates and Self‐Supporting Hydrogels

Peptide‐based hydrogels, originated by multiscale self‐assembling phenomenon, have been proposed as multivalent tools in different technological areas. Structural studies and molecular dynamics simulations pointed out the capability of completely aromatic peptides to gelificate if hydrophilic and hydrophobic forces are opportunely balanced. Here, the effect produced by the introduction of a Cys residue in the heteroaromatic sequence of (FY)3 and in its PEGylated variant was evaluated. The physicochemical characterization indicates that both FYFCFYF and PEG8‐FYFCFYF are able to self‐assemble in supramolecular nanostructures whose basic cross‐β motif resembles the one detected in the ancestor (FY)3 assemblies. However, gelification occurs only for FYFCFYF at a concentration of 1.5 wt%. After cross‐linking of cysteine residues, the hydrogel undergoes to an improvement of the rigidity compared to the parent (FY)3 assemblies as suggested by the storage modulus (G’) that increases from 970 to 3360 Pa. The mechanical properties of FYFCFYF are compatible with its potential application in bone tissue regeneration. Moreover, the avalaibility of a Cys residue in the middle of the peptide sequence could allow the hydrogel derivatization with targeting moieties or with biologically relevant molecules.