Proteases as molecular machines are known to drive a large array of fundamental processes in the body. While the presence of proteases can be probed with conventional techniques to measure genes and proteins, the ability to measure protease cleavage activity in living tissue is limited. Yet, we know proteases are regulated by a multitude of factors in their environment, including their concentration, spatial localization, availability of cofactors, and presence of regulators. In order to create a tool to measure proteases in the living tissue of the injured brain, we created a nanosensor that detects the protease calpain.