Molecular tension sensors: moving beyond force

Nearly all cellular processes are sensitive to mechanical inputs, and this plays a major role in diverse physiological processes. Mechanical stimuli are thought to be primarily detected through force-induced changes in protein structure. Approximately a decade ago, molecular tension sensors were created to measure forces across proteins within cells. Since then, an impressive assortment of sensors has been created and provided key insights into mechanotransduction, but comparisons of measurements between various sensors are challenging. In this review, we discuss the different types of molecular tension sensors, provide a system of classification based on their molecular-scale mechanical properties, and highlight how new applications of these sensors are enabling measurements beyond the magnitude of tensile load. We suggest that an expanded understanding of the functionality of these sensors, as well as integration with other techniques, will lead to consensus among measurements and critical insights into the underlying mechanisms of mechanotransduction.