To study the coordination between collectively migrating cells, the authors used cultured human umbilical vein endothelial cells (HUVECs), which model the collective endothelial cell migration that is associated with the formation of new blood vessels. Coupling between neighbouring cells was previously shown to depend on cadherin-based adherens junctions, which are known to be remodelled in migrating endothelial cells and often appear as serrated rather than smooth connections. In HUVECs expressing fluorescently tagged cadherin, both smooth and serrated junctions were observed. With respect to the direction of cell migration, the smooth junctions were typically present along lateral cell membranes, whereas serrated junctions consistently extended from the rear of the leader cells, overlapped with the front of their followers and formed finger-like structures. Three-dimensional structured-illumination microscopy and electron microscopy revealed that these 'cadherin fingers' appear as tubes, which comprise two lipid membrane bilayers with opposing curvatures and form through the engulfment by the follower cell of thin plasma membrane extensions from the leader cell.
Previous studies indicated that mechanical coupling between collectively migrating cells depends on actomyosin contractility. Inhibition or stimulation of actomyosin contractility in HUVECs perturbed or promoted cadherin finger formation, respectively. Further investigation showed the existence of a contractility gradient at sites of finger formation, with low contractility in the front of the follower cell and high contractility in the rear of the leader cell; this increased contractility of the leader cell's rear was then demonstrated to drive finger formation.
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