Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices.

TitleDynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices.
Publication TypeJournal Article
Year of Publication2015
AuthorsGjorevski, N, Piotrowski, AS, Varner, VD, Nelson, CM
JournalSci Rep
Volume5
Pagination11458
Date Published2015 07 13
ISSN2045-2322
KeywordsAnimals, Cell Culture Techniques, Cell Movement, Cells, Cultured, Collagen Type I, Extracellular Matrix, Gels, Humans, Image Processing, Computer-Assisted, Mice, Microscopy, Confocal, Models, Biological, Signal Transduction, Tensile Strength, Time-Lapse Imaging, Trans-Activators
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.

DOI10.1038/srep11458
Alternate JournalSci Rep
PubMed ID26165921
PubMed Central IDPMC4499882
Grant ListR21 HL118532 / HL / NHLBI NIH HHS / United States
U54 CA143803 / CA / NCI NIH HHS / United States
HL1100335 / HL / NHLBI NIH HHS / United States
R01 GM083997 / GM / NIGMS NIH HHS / United States
R01 HL120142 / HL / NHLBI NIH HHS / United States
CA128660 / CA / NCI NIH HHS / United States
HL118532 / HL / NHLBI NIH HHS / United States
U54CA143803 / CA / NCI NIH HHS / United States
R21 CA128660 / CA / NCI NIH HHS / United States
GM083997 / GM / NIGMS NIH HHS / United States
HL120142 / HL / NHLBI NIH HHS / United States