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.
Nature Cell Biology
We thank S. Cremer for statistical analysis, K. Hirsch for technical assistance, D. Critchley for talin1-deficient mice and R. Fässler for integrindeficient mice, discussions and critical reading of the manuscript. This work was supported by the German Research Foundation, the Peter Hans Hofschneider Foundation for Experimental Biomedicine, the Max Planck Society, the Alexander von Humboldt Foundation and the allergology programme of the Landesstiftung Baden-Württemberg.
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Renkawitz J, Schumann K, Weber M, et al. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 2009;11(12):1438-1443. doi:10.1038/ncb1992
Renkawitz, J., Schumann, K., Weber, M., Lämmermann, T., Pflicke, H., Piel, M., … Sixt, M. K. (2009). Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. Nature Publishing Group. https://doi.org/10.1038/ncb1992
Renkawitz, Jörg, Kathrin Schumann, Michele Weber, Tim Lämmermann, Holger Pflicke, Matthieu Piel, Julien Polleux, Joachim Spatz, and Michael K Sixt. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology. Nature Publishing Group, 2009. https://doi.org/10.1038/ncb1992.
J. Renkawitz et al., “Adaptive force transmission in amoeboid cell migration,” Nature Cell Biology, vol. 11, no. 12. Nature Publishing Group, pp. 1438–1443, 2009.
Renkawitz J, Schumann K, Weber M, Lämmermann T, Pflicke H, Piel M, Polleux J, Spatz J, Sixt MK. 2009. Adaptive force transmission in amoeboid cell migration. Nature Cell Biology. 11(12), 1438–1443.
Renkawitz, Jörg, et al. “Adaptive Force Transmission in Amoeboid Cell Migration.” Nature Cell Biology, vol. 11, no. 12, Nature Publishing Group, 2009, pp. 1438–43, doi:10.1038/ncb1992.