article published Jörg Renkawitz author 3F0587C8-F248-11E8-B48F-1D18A9856A870000-0003-2856-3369 Kathrin Schumann author F44D762E-4F9D-11E9-B64C-9EB26CEFFB5F Michele Weber author 3A3FC708-F248-11E8-B48F-1D18A9856A87 Tim Lämmermann author Holger Pflicke author Matthieu Piel author Julien Polleux author Joachim Spatz author Michael K Sixt author 41E9FBEA-F248-11E8-B48F-1D18A9856A870000-0002-6620-9179 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 Publishing Group2009 eng 10.1038/ncb1992 11121438 - 1443 yes Renkawitz, J., Schumann, K., Weber, M., Lämmermann, T., Pflicke, H., Piel, M., … Sixt, M. K. (2009). Adaptive force transmission in amoeboid cell migration. <i>Nature Cell Biology</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/ncb1992">https://doi.org/10.1038/ncb1992</a> J. Renkawitz, K. Schumann, M. Weber, T. Lämmermann, H. Pflicke, M. Piel, J. Polleux, J. Spatz, M.K. Sixt, Nature Cell Biology 11 (2009) 1438–1443. 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.” <i>Nature Cell Biology</i>. Nature Publishing Group, 2009. <a href="https://doi.org/10.1038/ncb1992">https://doi.org/10.1038/ncb1992</a>. J. Renkawitz <i>et al.</i>, “Adaptive force transmission in amoeboid cell migration,” <i>Nature Cell Biology</i>, 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.” <i>Nature Cell Biology</i>, vol. 11, no. 12, Nature Publishing Group, 2009, pp. 1438–43, doi:<a href="https://doi.org/10.1038/ncb1992">10.1038/ncb1992</a>. Renkawitz J, Schumann K, Weber M, et al. Adaptive force transmission in amoeboid cell migration. <i>Nature Cell Biology</i>. 2009;11(12):1438-1443. doi:<a href="https://doi.org/10.1038/ncb1992">10.1038/ncb1992</a> 39542018-12-11T12:06:05Z2021-01-12T07:53:27Z