Adaptive force transmission in amoeboid cell migration
Adaptive force transmission in amoeboid cell migration
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DOI：
10.1038/ncb1992
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发表时间：
2009-12-01
影响因子：
21.3
通讯作者：
Sixt, Michael
中科院分区：
文献类型：
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作者：
Renkawitz, Joerg;Schumann, Kathrin;Sixt, Michael
细胞的前端可以突出为不含肌动蛋白的膜泡，由肌动蛋白驱动的收缩力膨胀，也可以突出为富含肌动蛋白的伪足，聚合肌动蛋白丝将膜推出的位置（1-3）。如果扩张的肌动蛋白网络经历逆行的反作用力，推动细丝只能导致膜突出，这通常是由整联蛋白家族的跨膜受体提供的（4）。在这里，我们表明，趋化性树突状细胞机械地适应其基板的粘附性能之间的切换整合素介导的和整合素独立的运动。我们发现，在从事整合素-肌动蛋白离合器，肌动蛋白聚合完全变成突起，而在脱离肌动蛋白发生滑动和逆行流动。值得注意的是，加速逆行流动的平衡增加肌动蛋白聚合速率，因此，细胞形状和突起速度保持不变的交替基板。由于聚合动力学中的这种自适应响应，粘合剂基质的轨迹并不指示细胞的路径。相反，定向引导完全由化学引诱物的可溶性梯度提供，这赋予了这些“变形虫”细胞非凡的灵活性，使它们能够穿过几乎所有类型的组织。
The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane(1-3). Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family(4). Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue.