by Tina Czerwinski, Lars Bischof, David Böhringer, Sibel Kara, Pamela L. Strissel, Reiner Strick, Natalie Huhn, Alexander Winterl, Richard Gerum, Ernst Wittmann, Michael Schneider, Matthias W. Beckmann, Gina Nusser, Manuel Wiesinger, Silvia Budday, Anja Lux, Caroline Voskens, Ben Fabry, Christoph Mark
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.
Reference:
Tina Czerwinski, Lars Bischof, David Böhringer, Sibel Kara, Pamela L. Strissel, Reiner Strick, Natalie Huhn, Alexander Winterl, Richard Gerum, Ernst Wittmann, Michael Schneider, Matthias W. Beckmann, Gina Nusser, Manuel Wiesinger, Silvia Budday, Anja Lux, Caroline Voskens, Ben Fabry, Christoph MarkImmune cells employ intermittent integrin-mediated traction forces for 3D migrationIn Proceedings of the National Academy of Sciences, volume 123, 2026.
Bibtex Entry:
@article{czerwinski_immune_2026,
title = {Immune cells employ intermittent integrin-mediated traction forces for {3D} migration},
volume = {123},
issn = {0027-8424, 1091-6490},
url = {czerwinski 2026 PNAS.pdf},
doi = {10.1073/pnas.2524427123},
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.},
language = {en},
number = {11},
urldate = {2026-03-24},
journal = {Proceedings of the National Academy of Sciences},
author = {Czerwinski, Tina and Bischof, Lars and Böhringer, David and Kara, Sibel and Strissel, Pamela L. and Strick, Reiner and Huhn, Natalie and Winterl, Alexander and Gerum, Richard and Wittmann, Ernst and Schneider, Michael and Beckmann, Matthias W. and Nusser, Gina and Wiesinger, Manuel and Budday, Silvia and Lux, Anja and Voskens, Caroline and Fabry, Ben and Mark, Christoph},
month = mar,
year = {2026},
pages = {e2524427123},
file = {Full Text PDF:C:\Users\lovis\Zotero\storage\JVFQZ4KM\Czerwinski et al. - 2026 - Immune cells employ intermittent integrin-mediated traction forces for 3D migration.pdf:application/pdf},
}