October 9, 2007 | M. Poujade*, E. Grasland-Mongrain*, A. Hertzog†, J. Jouanneau†, P. Chavrier*, B. Ladoux*, A. Bugin*, and P. Silberzan*§
This study investigates the collective migration of an epithelial monolayer in response to a model wound. Using a microfabrication-based technique, researchers studied how a virgin surface can trigger collective motility in Madin-Darby canine kidney (MDCK) cells without damaging the cells. The study found that the release of a free surface is sufficient to initiate collective migration, which is independent of cell proliferation. The migration is characterized by a duality between collective and individual behaviors, with long-range velocity fields and active "leader cells" that precede a small cohort and destabilize the border through fingering instability. These leader cells develop a pluricellular actin belt, which may facilitate mechanical signaling between the leader and followers. Experiments with autocrine cells expressing hepatocyte growth factor (HGF) or in the presence of exogenous HGF showed higher average velocity of the border without leader cells.
The study also compared the migration of cells in different physiological situations, from morphogenesis to wound healing, highlighting common features in these processes. The microfabrication-based strategy offers advantages over traditional scratch assays, providing precise control over initial geometrical conditions and enabling parallel testing. The study found that the migration of cells is independent of the width of the initial strip, as long as it is larger than 150 µm. The average velocity of the border increased from 0 to 10 ± 5 µm·h⁻¹ over 15 hours. The migration was also found to be independent of cell proliferation, with cell divisions primarily occurring in the initial band of cells. The study also observed the roughening of the border and the emergence of leader cells, which are highly motile and exhibit a fibroblast-like appearance. These leader cells are not necessarily derived from the initial border but can arise from the first few rows of cells. The study also found that HGF can accelerate healing but suppress the fingering of the border, suggesting a different mechanism of action compared to mechanical triggering. The findings support the hypothesis of a mechanical means of communication between cells in response to the free surface. The study concludes that the microfabrication-based assay is an advantageous alternative to traditional scratch tests, offering precise control and parallel testing capabilities.This study investigates the collective migration of an epithelial monolayer in response to a model wound. Using a microfabrication-based technique, researchers studied how a virgin surface can trigger collective motility in Madin-Darby canine kidney (MDCK) cells without damaging the cells. The study found that the release of a free surface is sufficient to initiate collective migration, which is independent of cell proliferation. The migration is characterized by a duality between collective and individual behaviors, with long-range velocity fields and active "leader cells" that precede a small cohort and destabilize the border through fingering instability. These leader cells develop a pluricellular actin belt, which may facilitate mechanical signaling between the leader and followers. Experiments with autocrine cells expressing hepatocyte growth factor (HGF) or in the presence of exogenous HGF showed higher average velocity of the border without leader cells.
The study also compared the migration of cells in different physiological situations, from morphogenesis to wound healing, highlighting common features in these processes. The microfabrication-based strategy offers advantages over traditional scratch assays, providing precise control over initial geometrical conditions and enabling parallel testing. The study found that the migration of cells is independent of the width of the initial strip, as long as it is larger than 150 µm. The average velocity of the border increased from 0 to 10 ± 5 µm·h⁻¹ over 15 hours. The migration was also found to be independent of cell proliferation, with cell divisions primarily occurring in the initial band of cells. The study also observed the roughening of the border and the emergence of leader cells, which are highly motile and exhibit a fibroblast-like appearance. These leader cells are not necessarily derived from the initial border but can arise from the first few rows of cells. The study also found that HGF can accelerate healing but suppress the fingering of the border, suggesting a different mechanism of action compared to mechanical triggering. The findings support the hypothesis of a mechanical means of communication between cells in response to the free surface. The study concludes that the microfabrication-based assay is an advantageous alternative to traditional scratch tests, offering precise control and parallel testing capabilities.