Dual role of the nucleus in cell migration on planar substrates

Cell migration is essential to sustain life. There have been significant advances in the understanding of the mechanisms that control cell crawling, but the role of the nucleus remains poorly understood. The nucleus exerts a tight control of cell migration in 3D environments, but its influence in 2D migration on planar substrates remains unclear. Here, we study the role of the cell nucleus in 2D cell migration using a computational model of fish keratocytes. Our results indicate that the apparently minor role played by the nucleus emerges from two antagonist effects: While the nucleus modifies the spatial distributions of actin and myosin in a way that reduces cell velocity (e.g., the nucleus displaces myosin to the sides and front of the cell), its mechanical connection with the cytoskeleton alters the intracellular stresses promoting cell migration. Overall, the favorable effect of the nucleus-cytoskeleton connection prevails, which may explain why regular cells usually move faster than enucleated cells.