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

Nikolce Gjorevski,Alexandra S Piotrowski,Celeste M Nelson,Victor D Varner

doi:10.1038/srep11458

Nikolce Gjorevski, Alexandra S Piotrowski + Show 2 more

Open Access

https://doi.org/10.1038/srep11458

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Journal: Scientific Reports	Publication Date: Jul 13, 2015
Citations: 111	License type: CC BY 4.0

Affiliation: Princeton University

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.

Highlights

To measure matrix deformations and the corresponding mechanical forces that accompany collective cell migration, we monitored the motion of fluorescent beads embedded within the collagen surrounding the tissues
The migration bias disappeared (Fig. 5m,n), confirming that the directional cue was provided by ECM alignment and not soluble factors. These data indicate that matrix alignment plays two roles during collective migration: it increases the efficiency of migration and spatially directs migrating cohorts. These results reveal an essential and multifaceted role for endogenous mechanical forces during collective migration through 3D fibrillar matrices
We characterized and made quantitative estimates of the tensile forces that arise during this process, the nature and existence of which had only been inferred far[5]

Summary

Introduction

We set out to characterize the forces and ECM deformations arising during collective migration through physiological 3D matrices, which had not been fully elucidated previously

Methods

Results

Conclusion