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.

中文翻译：

---

Lamellipodium尖端肌动蛋白的倒刺末端用作力传感器。

细胞通过感知环境的刚性和牵引力来改变迁移的方向，但其潜在机制尚不清楚。在这里，我们显示了尖端肌动蛋白的倒刺末端在前缘充当了主动的“力传感器”。我们建立了一种通过弹性培养底物可视化细胞内单分子荧光肌动蛋白的方法。我们发现在细胞边缘拉伸后，肌动蛋白组装立即在lamellipodium尖端特别增加。肌动蛋白组装的速率随着拉伸速度的增加而增加。此外，在随后的保持步骤中，尖端肌动蛋白的聚合反应保持升高，这伴随着尖端带刺末端的负载减少。在没有WAVE复合物或Ena / VASP蛋白的情况下，仍然观察到拉伸诱导的末端肌动蛋白聚合。观察到的力与尖端肌动蛋白聚合之间的关系与布朗棘轮机制所预测的力-速度关系一致。拉伸导致相对于拉伸的基材额外的膜突出，并在30 s内使局部末端聚合增加了总细胞肌动蛋白的5％以上。我们的数据显示，lamellipodium尖端肌动蛋白组件的增加直接与负荷降低相关，这可以用作定向细胞突出的力传感器。