Calmodulin‐Based Dynamic Protein Hydrogels with Three Distinct Mechanical Stiffness.

Stimuli‐responsive hydrogels that leverage protein conformational changes are of significant interest in the design of dynamic materials applicable in a myriad of fields, such as drug delivery, actuators, biosensors, and microfluidics. The small calcium binding protein calmodulin (CaM), which undergoes three‐stage conformational changes upon successive binding with Ca2+ and specific ligands, offers a mechanism to create dynamic hydrogels with three distinct physical states. In this work, a CaM‐based recombinant protein hydrogel is engineered using [Ru(bpy)3]2+‐mediated photo‐crosslinking. This hydrogel displays the ability to reversibly increase its Young's modulus by 1.5‐fold and ∼7‐fold, respectively, upon binding with Ca2+ and subsequent interaction with trifluoperazine. The magnitude of stiffness changes is tunable by adjusting the length proportion of dynamic and static domains and modifying protein content. This tunable and reversible control over hydrogel mechanics is further utilized to engineer shape‐morphing materials, highlighting the versatile potential of this CaM‐based protein hydrogel for diverse applications. [ABSTRACT FROM AUTHOR]