Mechanics of Convective Cell Motion

Project Summary Collective cell motion is involved in diverse physiological and pathological processes, from the separation of tissues during early development, to tissue repair and cancer invasion in the adult. To date, collective motion is predominantly associated with the mechanisms and driving forces that underlie single cell migration. During migration, the cell undergoes a cyclic process of cell polarization and protrusion, adhesion to the extracellular matrix (ECM) and the generation of traction forces. Though the transmission of mechanical stresses at cell-cell junctions, the motion of a cell population becomes correlated over long distances and long times. However, cell- cell interactions can also accumulate large mechanical stresses in the form of tissue pressures and surface tensions. By force balance, gradients in these stresses can drive convection – mass transport due to bulk motion, as occurs in fluids. Further, as the forces that arise from gradients in tissue-scale surface tensions and pressure can be larger than those associated with single cell traction forces, ‘convective’ motions may be faster and more correlated that what can be achieved by migration alone. However, despite the potential generality of this phenomenon, how surface tension and pressure gradients are accumulated and transmitted within tissues is unclear. Further, how convection and migration coordinate their diverse timescales and lengthscales to yield complex cellular motions within is also unknown. This proposal seeks to identify the principles that underly convection, its coordination with migration, and its role in physiological processes. Identification of these principles will yield fundamental insights in biological mechanism, but also suggest novel targets for intervention in motility-associated diseases.