Immune cells employ intermittent integrin-mediated traction forces for 3D migration
Abstract
To reach targets outside the bloodstream, immune cells can extravasate and migrate through connective tissue. During tissue infiltration, immune cells migrate in an amoeboid fashion, characterized by weak matrix adhesions and low traction forces, that allows them to achieve high migration speeds of up to 10 µm/min. How immune cells reconcile amoeboid migration with the need to overcome steric hindrance in dense matrices is currently not understood. Here we show that NK92 (natural killer) cells can switch from their default amoeboid migration mode to a contractile, mesenchymal-like migration mode when moving through fibrous human amniotic membrane (HAM) tissue. We subsequently study immune cell migration in reconstituted 3D collagen networks with known mechanical properties and pore sizes and apply time-lapse confocal reflection microscopy to obtain simultaneous measurements of migration speed, directional persistence, and cell contractility. We find that NK92 cells exert substantial acto-myosin driven, integrin-mediated contractile forces of up to 100 nN on the extracellular matrix during short contractile phases. This burst-like contractile behavior is also found in primary B, T, NK cells, neutrophils, and monocytes, and is tightly related to the fraction of cells that become stuck in narrow pores of the surrounding matrix. Our results demonstrate that steric hindrance guides the rapid regulation of integrin-mediated adhesion to the ECM in a large number of immune cell subtypes.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (19)
Tina Czerwinski
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Lars Bischof
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
David Böhringer
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Sibel Kara
Department of Genetics, Friedrich-Alexander University Erlangen-Nürnberg
Pamela L. Strissel
Institute of Pathology, University Hospital Erlangen
Reiner Strick
Department of Gynecology and Obstetrics, University Hospital Erlangen
Natalie Huhn
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Alexander Winterl
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Richard Gerum
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Ernst Wittmann
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Michael Schneider
Department of Gynecology and Obstetrics, University Hospital Erlangen
Matthias W. Beckmann
Department of Gynecology and Obstetrics, University Hospital Erlangen
Gina Nusser
Department of Genetics, Friedrich-Alexander University Erlangen-Nürnberg
Manuel Wiesinger
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg
Silvia Budday
Department of Mechanical Engineering, Friedrich-Alexander University Erlangen-Nürnberg
Anja Lux
Department of Genetics, Friedrich-Alexander University Erlangen-Nürnberg
Caroline Voskens
Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nürnberg
Ben Fabry
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg
Christoph Mark
Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg