Extracting the Invisible from High-Content Live Cell Microscopy: Long-Range Inter-Cellular Communication in Collective Cell Migration

Cell biology imaging has entered the “big data” era. New technologies in microscopy and molecular biology produce high-content and multidimensional data sets encapsulating complex dynamic patterns that are inaccessible by human visual observation. One example is emergence of collective behavior in multi-cellular systems. From embryonic development, through synchronized beating of myocardiocytes to collective cell death - individual cells use basic cellular machinery to influence and respond to neighboring cells through a complex interplay of chemical and physical cues. How these local interactions are integrated in space and time to induce collective patterns is yet unknown. By designing and applying new analytical methods to migrating monolayers of epithelial cells, we discovered how local mechanical fluctuations induce long-range inter-cellular communication and identified potential molecular pathways driving this mechanism. We concluded that for effective collective migration contractility-mediating pathways must be optimally tuned to compromise between generation of motility forces and restriction of inter-cellular communication.