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Adaptive force transmission in amoeboid cell migration

2009; Nature Portfolio; Volume: 11; Issue: 12 Linguagem: Inglês

10.1038/ncb1992

1476-4679

Jörg Renkawitz, Kathrin Schumann, Michele Weber, Tim Lämmermann, Holger Pflicke, Matthieu Piel, Julien Polleux, Joachim P. Spatz, Michael Sixt,

Microtubule and mitosis dynamics

Migrating dendritic cells can adapt their adhesive properties to switch between integrin-dependent and -independent modes of migration. By modulating their actin polymerization dynamics, cells can maintain a steady migration speed through a changing environment. 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 membrane1,2,3. 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 family4. 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.