High Dynamic Range Probing of Single-Molecule Mechanical Force Transitions at Cell-Matrix Adhesion Bonds by a...

Mechanical signals in animal tissues are complex and rapidly changed, and how the force transduction emerges from the single-cell adhesion bonds remains unclear. DNA-based molecular tension sensors (MTS), albeit successful in cellular force probing, were restricted by their detection range and temporal resolution. Here, we introduced a plasmonic tension nanosensor (PTNS) to make straight progress toward these shortcomings. Contrary to the fluorescence-based MTS that only has specific force response thresholds, PTNS enabled the continuous and reversible force measurement from 1.1 to 48 pN with millisecond temporal resolution. We used the PTNS to visualize the high dynamic range single-molecule force transitions at cell-matrix adhesions during adhesion formation and migration. Time-resolved force traces revealed that the lifetime and duration of stepwise force transitions of molecular clutches are strongly modulated by the traction force through filamentous actin. The force probing technique is sensitive, fast, and robust and constitutes a potential tool for single-molecule and single-cell biophysics.