Programming Analytic, Mechanochemical Sensing and Response in Hydrogels with Biochemical Circuits

The dynamic nature of living organisms strongly relies on the transduction of mechanical forces into chemical signals, which is based on the conformational changes in proteins or macromolecular architectures to sense weak forces. Here we develop a modular chemomechanical system inspired by those in nature in which weak forces on hydrogels analytically control programmable chemical reaction networks. This system consists of two molecular modules: 1) tunable DNA force sensors and 2) cofactors that transduce force detection into different outputs. The DNA force sensors detect reversible hydrogel deformations without affecting a hydrogel’s mechanical moduli. During reversible deformations of a hydrogel, the hydrogel network could transfer force to DNA force sensors to dehybridize them, exposing a cryptic domain and thus reacting with different DNA complexes, i.e., cofactors to induce different downstream responses. With a DNA fluorophore-quencher reporter complex as cofactor, the DNA force sensor activation is detectable via fluorescence. Their output levels are precise and repeatable when either homogeneous or local forces are applied. With a partial transcriptional template as cofactor, the downstream DNA circuits can transduce, amplify, and broadcast force inputs. We anticipate that our programmable chemomechanical systems can serve as a general strategy for soft autonomous devices which respond to force across space and time.