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. Here, 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 β-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.We acknowledge the technical support from the Cell Culture Unit of Servei de Cultius Cel·lulars i Producció d’Anticossos i Citometria (SCAC) and of the Servei de Microscopia from Universitat Autònoma de Barcelona (UAB). F.P. acknowledges the Mizutani Foundation for Glycoscience (200077). M.S. and L.R.S. gratefully acknowledge financial support from MINECO (CTQ2017-89132-P) and the Generalitat de Catalunya (2017SGR1323).Peer reviewe