title: Rapid leukocyte migration by integrin-independent flowing and squeezing.
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.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Lämmermann
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Bader
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Monkley
authors.forename: Tim
authors.initials: T
authors.lastname: Worbs
authors.forename: Roland
authors.initials: R
authors.lastname: Wedlich-Söldner
authors.forename: Karin
authors.initials: K
authors.lastname: Hirsch
authors.forename: Markus
authors.initials: M
authors.lastname: Keller
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D024462:Myosin Type II / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D016023:Integrins; D024462:Myosin Type II