Mechanotransducing Hydrogel for Switching Enzyme Reactions through Modulation of Multivalent Salt-Bridge Interactions

Mechanoresponsive materials can harness mechanical forces to initiate molecular events and alter their physicochemical properties. Enzyme reactions, which enable diverse chemical transformations under mild conditions, have great potential as outputs of the mechanoresponse, especially in biological applications. Here, we present a hydrogel-based platform that realizes mechanotransduction to enzyme reactions through the modulation of multivalent salt-bridge interactions between a polymeric inhibitor incorporated within the gel network and an enzyme in the gel matrix. As a proof-of-concept study, two types of hydrogels were developed: ^BGGu-gel with β-galactosidase and ^TBGu-gel with thrombin. The ^BGGu-gel, containing a chromogenic substrate, exhibits mechanochromism, visually mapping the mechanical load onto the gel via a colorimetric response. The ^TBGu-gel, containing fibrinogen as a substrate, displays self-growth, achieving enhanced mechanical strength under stress through thrombin-mediated hydrolysis of fibrinogen into fibrin, followed by the spontaneous formation of fibrin fibers as an additional gel network.