Chen Tianchi, Callan-Jones Andrew, Fedorov Eduard, Ravasio Andrea, Brugués Agustí, Ong Hui Ting, Toyama Yusuke, Low Boon Chuan, Trepat Xavier, Shemesh Tom, Voituriez Raphaël, Ladoux Benoît
Mechanobiology Institute, National University of Singapore, Singapore.
Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS and Université Paris Diderot, Paris, France.
Nat Phys. 2019 Apr;15:393-402. doi: 10.1038/s41567-018-0383-6. Epub 2019 Jan 21.
Cell migration over heterogeneous substrates during wound healing or morphogenetic processes leads to shape changes driven by different organizations of the actin cytoskeleton and by functional changes including lamellipodial protrusions and contractile actin cables. Cells distinguish between cell-sized positive and negative curvatures in their physical environment by forming protrusions at positive ones and actin cables at negative ones; however, the cellular mechanisms remain unclear. Here, we report that concave edges promote polarized actin structures with actin flow directed towards the cell edge, in contrast to well-documented retrograde flow at convex edges. Anterograde flow and contractility induce a tension anisotropy gradient. A polarized actin network is formed, accompanied by a local polymerization-depolymerization gradient, together with leading-edge contractile actin cables in the front. These cables extend onto non-adherent regions while still maintaining contact with the substrate through focal adhesions. The contraction and dynamic reorganization of this actin structure allows forward movements enabling cell migration over non-adherent regions on the substrate. These versatile functional structures may help cells sense and navigate their environment by adapting to external geometric and mechanical cues.
在伤口愈合或形态发生过程中，细胞在异质底物上迁移会导致形状变化，这是由肌动蛋白细胞骨架的不同组织以及包括片状伪足突起和收缩性肌动蛋白束在内的功能变化驱动的。细胞通过在正曲率处形成突起，在负曲率处形成肌动蛋白束来区分其物理环境中细胞大小的正曲率和负曲率；然而，细胞机制仍不清楚。在这里，我们报告凹边促进极化的肌动蛋白结构，肌动蛋白流指向细胞边缘，这与凸边有充分记录的逆行流相反。顺行流和收缩性诱导张力各向异性梯度。形成了极化的肌动蛋白网络，伴随着局部聚合 - 解聚梯度，以及前方边缘收缩性肌动蛋白束。这些束延伸到非粘附区域，同时仍通过粘着斑与底物保持接触。这种肌动蛋白结构的收缩和动态重组允许向前运动，使细胞能够在底物上的非粘附区域迁移。这些多功能的功能结构可能通过适应外部几何和机械线索来帮助细胞感知和在其环境中导航。
