Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices. Author Nikolce Gjorevski, Alexandra Piotrowski, Victor Varner, Celeste Nelson Publication Year 2015 Type Journal Article Abstract Collective cell migration drives tissue remodeling during development, wound repair, and metastatic invasion. The physical mechanisms by which cells move cohesively through dense three-dimensional (3D) extracellular matrix (ECM) remain incompletely understood. Here, we show directly that migration of multicellular cohorts through collagenous matrices occurs via a dynamic pulling mechanism, the nature of which had only been inferred previously in 3D. Tensile forces increase at the invasive front of cohorts, serving a physical, propelling role as well as a regulatory one by conditioning the cells and matrix for further extension. These forces elicit mechanosensitive signaling within the leading edge and align the ECM, creating microtracks conducive to further migration. Moreover, cell movements are highly correlated and in phase with ECM deformations. Migrating cohorts use spatially localized, long-range forces and consequent matrix alignment to navigate through the ECM. These results suggest biophysical forces are critical for 3D collective migration. Keywords Trans-Activators, Animals, Mice, Extracellular Matrix, Humans, Models, Biological, Signal Transduction, Image Processing, Computer-Assisted, Cells, Cultured, Microscopy, Confocal, Cell Movement, Time-Lapse Imaging, Cell Culture Techniques, Collagen Type I, Gels, Tensile Strength Journal Sci Rep Volume 5 Pages 11458 Date Published 2015 Jul 13 ISSN Number 2045-2322 DOI 10.1038/srep11458 Alternate Journal Sci Rep PMCID PMC4499882 PMID 26165921 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML