Unraveling the Dual-Stretch-Mode Impact on Tension Gauge Tethers' Mechanical Stability

Tension gauge tethers (TGTs), short DNA segments serving as extracellular tension sensors, are instrumental in assessing the tension dynamics in mechanotransduction. These TGTs feature an initial shear-stretch region and an unzip-stretch region. Despite their utility, no theoretical model has been available to estimate their tension-dependent lifetimes [τ(f)], restricting insights from cellular mechanotransduction experiments. We have now formulated a concise expression for τ(f) of TGTs, accommodating contributions from both stretch regions. Our model uncovers a tension-dependent energy barrier shift occurring when tension surpasses a switching force of approximately 13 pN for the recently developed TGTs, greatly influencing τ(f) profiles. Experimental data from several TGTs validated our model. The calibrated expression can predict τ(f) of TGTs at 37 °C based on their sequences with minor fold changes, supporting future applications of TGTs.