Stochastic methods for inferring states of cell migration

Cell migration refers to the ability of cells to translocate across a substrate or through a matrix. To achieve net movement requires spatiotemporal regulation of the actin cytoskeleton. Computational approaches are neceary to identify and quantify the regulatory mechanisms that generate directed cell movement. To address this need, we developed computational tools, based on stochastic modeling, to analyze time series data for the position of randomly migrating cells. Our approach allows parameters that characterize cell movement to be efficiently estimated from time series data. We applied our methods to analyze the random migration of Mouse Embryonic Fibroblasts (MEFS). Our analysis revealed that these cells exist in two distinct states of migration characterized by differences in cell speed and persistence. Further analysis revealed that the Rho-family GTPase RhoG plays a role in establishing these two states. An important feature of our computational approach is that it provides a method for predicting the current migration state of an individual cell from time series data. Using this feature, we demonstrate that HeLa cells also exhibit two states of migration, and that these states correlate with differences in the spatial distribution of active Rac1.