Lamellipodium tip actin barbed ends serve as a force sensor

Abstract

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.