Abstract

Hepatocyte growth factor (HGF) induces cell migration and scattering by mechanisms that are thought to tip a local balance of competing physical forces; cell-to-cell and cell-to-substrate forces. In this local process, HGF is known to attenuate local cadherin-dependent adhesion forces for cell-cell junction development and enhance local integrin-dependent contractile forces for pulling neighboring cells apart. Here we use an expanding island of confluent Madin-Darby canine kidney (MDCK) cells as a model system to quantify the collective cell migration. In the absence of HGF, cell trajectories are highly tortuous whereas in the presence of HGF, they become far less so, resembling free expansion of a gas. At the level of cell-to-cell junctions, HGF attenuates the linkage of stress fibers to cell-to-cell junctions with concomitant decrease in intercellular stress. At the level of cell-to-substrate junctions, HGF augments the linkage of stress fibers to cell-to-substrate junctions with no apparent effect on traction. Together, HGF induces both structural changes in the actin-bound junctional protein complex and physical forces spanning multicellular clusters, which further promotes the expansion of confluent cellular layer.

Highlights

  • Transmitted within the cell layer itself across cell-cell junctions

  • Based on the reduced magnitude and greater fluctuations in contractile tension caused by HGF, we hypothesized that HGF could directly alter cadherin-mediated adherens junctions (AJs) and actin filaments (AFs)[18]

  • The tension in the cellular island is intimately associated with focal adhesion (FA) dynamics[19]

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Summary

Introduction

Transmitted within the cell layer itself across cell-cell junctions. These biophysical quantities were complemented by mapping of the distribution of f-actin, E-cadherin, and vinculin. Cellular trajectories were measured from displacement fields over 12 hours to identify differences in motion between the control and the HGF-treated island (Fig. 1b). Distribution of speed, traction and tension in the cellular islands during the monolayer expansion.

Results
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