Lamellipodium tip actin barbed ends serve as a force sensor

Cells change direction of migration by sensing rigidity of environment and traction force, yet its underlying mechanism is unclear. Here, we show that tip actin barbed ends serve as an active “force sensor” at the leading edge. We established a method to visualize intracellular single‐molecule fluorescent actin through an elastic culture substrate. We found that immediately after cell edge stretch, actin assembly increased specifically at the lamellipodium tip. The rate of actin assembly increased with increasing stretch speed. Furthermore, tip actin polymerization remained elevated at the subsequent hold step, which was accompanied by a decrease in the load on the tip barbed ends. Stretch‐induced tip actin polymerization was still observed without either the WAVE complex or Ena/VASP proteins. The observed relationships between forces and tip actin polymerization are consistent with a force–velocity relationship as predicted by the Brownian ratchet mechanism. Stretch caused extra membrane protrusion with respect to the stretched substrate and increased local tip polymerization by >5% of total cellular actin in 30 s. Our data reveal that augmentation of lamellipodium tip actin assembly is directly coupled to the load decrease, which may serve as a force sensor for directed cell protrusion. Cell edge stretch was found to promote the leading‐edge actin assembly. This reaction is fast and does not require the major actin polymerizing factors. Based on the single‐molecule speckle microscopy analysis of actin assembly and its comparison with mathematical modeling, the authors propose that actin barbed ends in contact with the lamellipodium tip serve as an actin retrograde flow‐assisted, Brownian ratchet‐based force sensor to drive cell protrusion in the direction of traction force.