Mechanotransduction, the process by which cells respond to tension transmitted through various supramolecular linkages, is important for understanding cellular behavior. Tension gauge tethers (TGTs), short fragments of double-stranded DNA that irreversibly break under shear-stretch conditions, have been used in live cell experiments to study mechanotransduction. However, our current understanding of TGTs’ mechanical responses is limited, which limits the information that can be gleaned from experimental observations. In this study, we quantified the tension-dependent lifetime of TGTs to better understand their mechanical stability under various physiologically relevant stretching conditions. This work has broad applications for using TGTs as tension threshold and duration sensors and also suggests the need to revisit previous interpretations of experimental observations.

Mechanotransduction of cells, a time-taking process, relies on responding to tension transmitted along various supramolecular linkages. The minimal lifetimes of the linkages needed for proper mechanotransduction remain poorly understood. We propose that such information can be provided using tension-dependent lifetime sensors that undergo irreversible tension-dependent dissociation. We quantified the tension-dependent lifetime of DNA-based Tension Gauge Tethers. Comparing it with the observations from previous cell studies, the minimal lifetime of individual integrin-RGD linkage needed for cell spreading was determined to be tens of seconds over the physiological tension range.