July 10th- 21st, 2017 | IFOM, Milan - Italy
Collective cell migration refers to the process of many cells migrating as a cohesive group with each individual cell correlating its own movement with that of its neighbors. It is an emergent phenomenon at multicellular level and an inherent part of a developing embryo, a healing wound, a regenerating tissue and a progressing cancer. For example, an increasingly recognized mode of tumor dissemination is through collective migratory/invasive strategies. Under these conditions, tumor cell sheets and strands, or isolated cell cohorts invade the surrounding stroma, gain access to vessels, where collective assemblies of cancerous cells have been shown to resist attrition and to display increased metastatic potential. In this dynamical process, tumor cells interact with the microenvironment and with neighboring tumor cells by exchanging chemical signals and by exerting physical forces. The ability to switch between diverse modes of individual and collective migration enables tumors to adapt to micro-environmental conditions and to metastasize.
One framework to conceptualize the motion of living collective is to equate it to inert particles systems and use basic physical law typically describing soft matter dynamics. For example, recent advances have established that a variety of multicellular entities acquire structural and dynamic physical properties that are surprisingly similar to glassy materials. During collective motility within confluent monolayers cell sheets can flow like a fluid, but as density rises due to proliferation the motion of each cells is constrained by the crowding due to its neighbors, forcing them to move in groups. At a critical density, motility ceases and collectives jam or rigidify undergoing a liquid-to-solid-like transition, surprisingly similar to what is observed in systems of inert particles that undergo a jamming transition at large density. The unjammed-to-jammed transition has been proposed as a general framework to describe collective behavior in cells.
We will reproduce and analyze this transition and explore some of its kinematic features using a simplified in vitro system of cell of epithelial origin, which when seeded in culture dish form monolayers held together by tight cell-cell interactions. As the cells within monolayers divide, they also undergo dramatic kinematic changes before ceasing migration that can be captured through time-lapse microscopy and analyzed using approaches more commonly employed to describe the behavior of inert matter.