Confinement and substrate topography control 3D cell migration*

Cell movement in vivo is often characterized by strong confinement and heterogeneous, three-dimensional environments. Such external constraints on cell motility are known to play important roles in many vital processes, e.g. during development, differentiation, and the immune response, as well as in threatening pathologies like cancer metastasis. A three-dimensional computational modeling framework that describes a lamellipodium-based motion of cells in arbitrarily shaped and topographically structured external surroundings is developed. It includes the in vitro model systems that are currently studied experimentally: like well-designed modulations of surface topography, cells in vertical confinement, in microchannels and on fibers. While other modes of motion beyond lamellipodia are often triggered by the confinement, our model can serve as a benchmark to explore this specific motility mode and its interaction with the environment in depth. Both topographical features and confinement modulate the cell's speed, shape, actin organization and can induce changes in direction along preferred axes defined by the constraints.It is also found that substrate curvature (with radii of the order of the cell size and below) affect the speed of migration and can even impede motion.