Title | Dynamic tensile forces drive collective cell migration through three-dimensional extracellular matrices. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Gjorevski, N, Piotrowski, AS, Varner, VD, Nelson, CM |
Journal | Sci Rep |
Volume | 5 |
Pagination | 11458 |
Date Published | 2015 Jul 13 |
ISSN | 2045-2322 |
Keywords | Animals, 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 | <p>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. </p> |
DOI | 10.1038/srep11458 |
Alternate Journal | Sci Rep |
PubMed ID | 26165921 |
PubMed Central ID | PMC4499882 |
Grant List | R21 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 |