Rapid leukocyte migration by integrin-independent flowing and squeezing

Tim Lämmermann, Bernhard L. Bader, Susan J. Monkley, Tim Worbs, Roland Wedlich-Söldner, Karin Hirsch, Markus Keller, Reinhold Förster, David R. Critchley, Reinhard Fässler and Michael Sixt ()
Additional contact information
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,

Nature, 2008, vol. 453, issue 7191, 51-55

Abstract: 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.

Date: 2008
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DOI: 10.1038/nature06887

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