Enzyme Induced Stiffening of Nanoparticle–Hydrogel Composites with Structural Color

The passive monitoring of biological environments by soft materials has a variety of nanobiotechnology applications; however, invoking distinct transitions in geometric, mechanical or optical properties remains a prevalent design challenge. We demonstrate here that close-packed nanoparticle-hydrogel composites can progress through a substantial shift in such properties by the use of a chemical-to-physical cross-link transition mediated by the catalytic activity of different proteases. Catalytic cleavage of the original hydrogel network structure initiates the self-assembled formation of a secondary, physically cross-linked network, causing a 1200% increase in storage modulus. Furthermore, this unique mechanism can be fabricated as a 3D photonic crystal with broad (∼240 nm), visible responses to the targeted enzymes. Moreover, the material provided threshold responses, requiring a certain extent of proteolytic activity before the transition occurred. This allowed for the fabrication of Boolean logic gates (OR and AND), which responded to a specific assortment of proteases. Ultimately, this mechanism enables the design of stimuli-responsive hydrogels, which can proceed through a secondary network formation, after an energetic barrier has been breached. Protease responsive hydrogel nanocomposites, described here, could offer avenues in degradation-stiffening and collapsing materials for a variety of biomaterial applications.