title: Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices.
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.
authors.affiliation: Department of Chemical &Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Nikolce
authors.initials: N
authors.lastname: Gjorevski
authors.affiliation: Department of Chemical &Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Piotrowski
authors.affiliation: Department of Chemical &Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Victor D
authors.initials: VD
authors.lastname: Varner
authors.affiliation: 1] Department of Chemical &Biological Engineering, Princeton University, Princeton, NJ 08544, USA [2] Department of Molecular Biology Princeton University, Princeton, NJ 08544.
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Nelson
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism*; D005782:Gels / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D018613:Microscopy, Confocal; D008954:Models, Biological; D015398:Signal Transduction; D013718:Tensile Strength; D059008:Time-Lapse Imaging; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005782:Gels; C511173:Mrtfa protein, mouse; D015534:Trans-Activators