Weak force stalls protrusion at the leading edge of the lamellipodium

Weak force stalls protrusion at the leading edge of the lamellipodium
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DOI:
10.1529/biophysj.105.064600
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发表时间:
2006-03-01
影响因子:
3.4
通讯作者:
Verkhovsky, AB
Verkhovsky, AB
中科院分区:
生物学3区
文献类型:
--
作者:
Bohnet, S;Ananthakrishnan, R;Verkhovsky, AB

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细胞迁移的第一步是由肌动蛋白聚合和细胞前缘的粘附驱动的。聚合和粘合力已经被估计,但净突出力尚未被准确测量。我们逮捕了一个移动的鱼类角膜细胞的前缘与流体动力学负载所产生的流体流动从微量移液管。当细胞接近移液管时,流动停止局部突起,导致弧形凹陷和前缘向上折叠。移液器移除后,流动的影响是可逆的,并取决于流动方向,这表明它是外力的直接影响,而不是受调节的细胞反应。流体流动的建模给出了令人惊讶的低值,仅为每微米几皮牛顿的制动力。增强的相差,荧光和干涉反射显微镜表明,流动不废除肌动蛋白聚合,并没有破坏逮捕前形成的粘连,而是干扰弱新生的粘连在细胞的最前面。我们的结论是,一个弱的外力是足以重新定位不断增长的肌动蛋白网络的领先优势,并停止突起。
Protrusion, the first step of cell migration, is driven by actin polymerization coupled to adhesion at the cell's leading edge. Polymerization and adhesive forces have been estimated, but the net protrusion force has not been measured accurately. We arrest the leading edge of a moving fish keratocyte with a hydrodynamic load generated by a fluid flow from a micropipette. The flow arrests protrusion locally as the cell approaches the pipette, causing an arc-shaped indentation and upward folding of the leading edge. The effect of the flow is reversible upon pipette removal and dependent on the flow direction, suggesting that it is a direct effect of the external force rather than a regulated cellular response. Modeling of the fluid flow gives a surprisingly low value for the arresting force of just a few piconewtons per micrometer. Enhanced phase contrast, fluorescence, and interference reflection microscopy suggest that the flow does not abolish actin polymerization and does not disrupt the adhesions formed before the arrest but rather interferes with weak nascent adhesions at the very front of the cell. We conclude that a weak external force is sufficient to reorient the growing actin network at the leading edge and to stall the protrusion.