Renkawitz Jörg, Schumann Kathrin, Weber Michele, Lämmermann Tim, Pflicke Holger, Piel Matthieu, Polleux Julien, Spatz Joachim P, Sixt Michael
Max Planck Institute of Biochemistry, Hofschneider Group Leukocyte Migration, 82152 Martinsried, Germany.
Nat Cell Biol. 2009 Dec;11(12):1438-43. doi: 10.1038/ncb1992. Epub 2009 Nov 15.
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. 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. 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.
一种是作为无肌动蛋白的膜泡突出，该膜泡由肌动球蛋白驱动的收缩力充气；另一种是作为富含肌动蛋白的伪足突出，在伪足部位，聚合的肌动蛋白丝将膜推出。只有当扩展的肌动蛋白网络受到逆行反作用力时，推动的肌动蛋白丝才能使膜突出，这种反作用力通常由整合素家族的跨膜受体提供。在这里，我们表明趋化性树突状细胞通过在整合素介导的运动和不依赖整合素的运动之间切换，在机械上适应其底物的粘附特性。我们发现，当激活整合素 - 肌动蛋白连接时，肌动蛋白聚合完全转化为突出，而在脱离连接时，肌动蛋白发生滑动和逆行流动。值得注意的是，加速的逆行流动被增加的肌动蛋白聚合速率所平衡；因此，在交替的底物上，细胞形状和突出速度保持恒定。由于聚合动力学中的这种适应性反应，粘附底物的轨迹并不决定细胞的路径。相反，定向引导完全由趋化因子的可溶性梯度提供，这赋予这些“阿米巴样”细胞非凡的灵活性，使它们能够穿过几乎每一种类型的组织。
