1. Department of Molecular Medicine,
2. Junior Research Group Cellular Dynamics and Cell Patterning, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
3. Department of Nutritional Medicine, Technische Universität München, Munich, 85350 Freising, Germany
4. Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK
5. Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany

Correspondence to: Michael Sixt¹ Correspondence and requests for materials should be addressed to M.S. (Email: sixt@biochem.mpg.de).

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.

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