Pharmacological regulation of protein-polymer hydrogel stiffness

The extracellular matrix (ECM) undergoes constant physiochemical change. User-programmable biomaterials afford exciting opportunities to study such dynamic processes in vitro . Herein, we introduce a protein-polymer hydrogel whose stiffness can be pharmacologically and reversibly regulated with conventional antibiotics. Specifically, a coumermycin-mediated homodimerization of gel-tethered DNA gyrase subunit B (GyrB) creates physical crosslinking and a rheological increase in hydrogel mechanics, while competitive displacement of coumermycin with novobiocin returns the material to its softened state. These unique platforms could potentially be modulated in vivo and are expected to prove useful in elucidating the effects of ECM-presented mechanical signals on cell function. Hydrogel biomaterials partially modified with GyrB can be stiffened/softened via small molecule pharmacological-mediated protein (de)dimerization.