Enzyme-substrate interactions promote the self-assembly of amino acid derivatives into supramolecular hydrogels.

Abstract

Enzyme-responsive supramolecular hydrogels are a new class of smart materials and have enormous potential to be used in biology and medicine. In this study, α-chymotrypsin was proposed to promote the self-assembly of amino acid derivatives for the preparation of such supramolecular hydrogels. It is found that α-chymotrypsin significantly shortens the gelation time from 8 days (or no gelation occurred within 2 weeks) to 10 min-4 h depending on the structure of amino acid derivatives. The chemical compositions and microstructures of the hydrogels were further investigated by LC-MS, microscopy and spectroscopy techniques. The results show that the transparent hydrogels consist of long nanofibers with approximately 20 nm in diameter. These nanofibers are composed of Fmoc-amino acid and amino acid, which were formed from the hydrolysis of amino acid ester, with a molar ratio of 4.346 : 1 (Fmoc-F/F) and 0.548 : 1 (Fmoc-F/Y), respectively. Furthermore, the molecular simulation was performed to investigate the specific recognition of α-chymotrypsin to amino acid derivatives. The results indicate that the enzyme-substrate interactions are responsible for promoting the supramolecular self-assembly of these amino acid derivatives into fibrous hydrogels. In addition to being the first example of enzyme-substrate interaction-promoted supramolecular self-assembly, this novel concept opens up the possibility of making use of various enzymes and their substrates (or analogues) in the discovery of new supramolecular materials with enzyme responsiveness.