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Rapid leukocyte migration by integrin-independent flowing and squeezing

Author

Listed:
  • Tim Lämmermann

    (Department of Molecular Medicine,)

  • Bernhard L. Bader

    (Technische Universität München, Munich, 85350 Freising, Germany)

  • Susan J. Monkley

    (University of Leicester)

  • Tim Worbs

    (Institute of Immunology, Hannover Medical School)

  • Roland Wedlich-Söldner

    (Junior Research Group Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany)

  • Karin Hirsch

    (Department of Molecular Medicine,)

  • Markus Keller

    (Technische Universität München, Munich, 85350 Freising, Germany)

  • Reinhold Förster

    (Institute of Immunology, Hannover Medical School)

  • David R. Critchley

    (University of Leicester)

  • Reinhard Fässler

    (Department of Molecular Medicine,)

  • Michael Sixt

    (Department of Molecular Medicine,)

Abstract

All metazoan cells carry transmembrane receptors of the integrin family, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In agreement with this principle, rapidly migrating leukocytes use integrin-mediated adhesion when moving over two-dimensional surfaces. As migration on two-dimensional substrates naturally overemphasizes the role of adhesion, the contribution of integrins during three-dimensional movement of leukocytes within tissues has remained controversial. We studied the interplay between adhesive, contractile and protrusive forces during interstitial leukocyte chemotaxis in vivo and in vitro. We ablated all integrin heterodimers from murine leukocytes, and show here that functional integrins do not contribute to migration in three-dimensional environments. Instead, these cells migrate by the sole force of actin-network expansion, which promotes protrusive flowing of the leading edge. Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus.

Suggested Citation

  • Tim Lämmermann & Bernhard L. Bader & Susan J. Monkley & Tim Worbs & Roland Wedlich-Söldner & Karin Hirsch & Markus Keller & Reinhold Förster & David R. Critchley & Reinhard Fässler & Michael Sixt, 2008. "Rapid leukocyte migration by integrin-independent flowing and squeezing," Nature, Nature, vol. 453(7191), pages 51-55, May.
    • Handle: RePEc:nat:nature:v:453:y:2008:i:7191:d:10.1038_nature06887
    DOI: 10.1038/nature06887
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    Cited by:

    1. Oliver Nagel & Can Guven & Matthias Theves & Meghan Driscoll & Wolfgang Losert & Carsten Beta, 2014. "Geometry-Driven Polarity in Motile Amoeboid Cells," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-20, December.
    2. Parthasarathy Srinivasan & Ioannis K Zervantonakis & Chandrasekhar R Kothapalli, 2014. "Synergistic Effects of 3D ECM and Chemogradients on Neurite Outgrowth and Guidance: A Simple Modeling and Microfluidic Framework," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-15, June.
    3. Florian Geiger & Daniel Rüdiger & Stefan Zahler & Hanna Engelke, 2019. "Fiber stiffness, pore size and adhesion control migratory phenotype of MDA-MB-231 cells in collagen gels," PLOS ONE, Public Library of Science, vol. 14(11), pages 1-13, November.
    4. F. O. Ribeiro & M. J. Gómez-Benito & J. Folgado & P. R. Fernandes & J. M. García-Aznar, 2017. "Computational model of mesenchymal migration in 3D under chemotaxis," Computer Methods in Biomechanics and Biomedical Engineering, Taylor & Francis Journals, vol. 20(1), pages 59-74, January.

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