pH-Responsive Self-Assembly of Amyloid Fibrils for Dual Hydrolase-Oxidase Reactions

There is an increasing interest in synthetic systems that can execute bioinspired chemical reactions without requiring the complex structures that characterize enzymes in their components. The hierarchical self-assembly of peptides provides a means to create catalytic microenvironments. Ideally, as it occurs in enzymes, the catalytic activity of peptide nanostructures should be reversibly regulated. In a typical enzyme mimetic design, the peptide's self-assembling and catalytic activities are segregated into different regions of the sequence. Her; we aimed to design minimal peptides in which the self-assembly and function were all encoded in the same amino acids. Moreover, we wanted to endow the resulting one-component nanomaterial with divergent, chemically unrelated, catalytic activities, a property not observed in natural enzymes. We show that short peptides consisting only of histidine and tyrosine residues, arranged in a binary pattern, form biocompatible amyloid-like fibrils and hydrogels combining hydrolytic and electrocatalytic activities. The nanofibers' mesoscopic properties are controlled by pH, the transition between assembled active beta-sheet fibrils, and disassembled inactive random coil species occurring in a physiologically relevant pH range. The structure of one of such amyloid-like fibrils, as derived from molecular dynamic simulations, provides insights on how they attain this combination of structural and catalytic properties.

Automated summary

Researchers have designed a new type of peptide nanomaterial consisting solely of histidine and tyrosine residues, which exhibit biocompatible amyloid-like fibrils and hydrogels with hydrolytic and electrocatalytic activities. These nanofibers show controllable mesoscopic properties at different pH levels, transitioning between active beta-sheet fibrils and inactive random coil species. The structural insights derived from molecular dynamic simulations offer understanding on how these amyloid-like fibrils achieve a combination of structural and catalytic properties.