Calcium-responsive hydrogels enabled by inducible protein-protein interactions

The inherent complexity of cell-matrix interactions calls for smart materials that can actively sense and respond to environmental stimuli with physiological relevance. Here we demonstrate the creation of entirely protein-based Ca2+-responsive hydrogels by covalently assembling calmodulin (CaM) and its cognate ligand, M13-peptide, using SpyTag/SpyCatcher chemistry. The resulting protein hydrogels comprising CaM and M13 exhibited mechanics and stability dependent on Ca2+, an important second messenger in biology, as well as suitability for 3D cell culturing. These results demonstrate the feasibility of using inducible protein-protein interactions to design biomaterials with dynamic properties, providing new opportunities for materials biology.