Molecular Tension Sensors Report Forces Generated by Single Integrin Molecules in Living Cells

TLDR

Living cells respond to mechanical cues, but how they generate and sense force is poorly understood because no method visualizes cell‑generated forces at the molecular scale. The study introduces FRET‑based molecular tension sensors that enable direct visualization of cell‑generated forces with single‑molecule sensitivity. These sensors were applied to map the distribution of forces exerted by individual integrins, key adhesion molecules involved in cell and developmental biology. The data reveal complex tension patterns within focal adhesions and show that modest molecular tensions are sufficient to support robust cellular adhesion.

Abstract

Living cells are exquisitely responsive to mechanical cues, yet how cells produce and detect mechanical force remains poorly understood due to a lack of methods that visualize cell-generated forces at the molecular scale. Here we describe Förster resonance energy transfer (FRET)-based molecular tension sensors that allow us to directly visualize cell-generated forces with single-molecule sensitivity. We apply these sensors to determine the distribution of forces generated by individual integrins, a class of cell adhesion molecules with prominent roles throughout cell and developmental biology. We observe strikingly complex distributions of tensions within individual focal adhesions. FRET values measured for single probe molecules suggest that relatively modest tensions at the molecular level are sufficient to drive robust cellular adhesion.