In vivo, cells exist in a complex mechanical environment that is a source of applied forces and a means of mechanical support. Cells respond to these mechanical stimuli through a poorly understood process called mechanotransduction. A clearer understanding of this process will lead to improved methods for manipulating cell behavior, both in the contexts of engineered tissue constructs as well as in mechanically sensitive diseases, such as cancer and fibrosis. As mechanotransduction is likely due to force-induced conformation changes in load-bearing proteins, we develop and use genetically encoded protein-based biosensors that exhibit force-dependent changes in the color of emitted light. This technology enables dynamic measurements of mechanical forces at the molecular level inside living cells. Furthermore, this approach is innately compatible with concepts and approaches common in molecular biology and biophysics, enabling mechanistic studies of mechanotransduction. In this talk, I will discuss how we have been expanding this technology to (1) create sensors with improved and broader functionality, (2) understand how force alters protein activity and turnover dynamics to control cellular processes, such as directed cell migration, and (3) elucidate force-sensitive protein localization and complex formation to increase the understanding of mechanisms of mechanotransduction.
Brenton D. Hoffman (2026) studied this question.