Multicompartment cell-based modeling of confined migration: regulation by cell intrinsic and extrinsic factors

Though cell and nuclear deformability are expected to influence efficiency of confined migration, their individual and collective influence on migration efficiency remains incompletely understood. In addition to cell intrinsic properties, the relevance of cell extrinsic factors on confined migration, if any, has not been adequately explored. Here we address these questions using a statistical mechanics- based stochastic modeling approach where cell/ nuclear dimensions and their deformability are explicitly taken into consideration. In addition to demonstrating the importance of cell softness in sustaining confined migration, our results suggest that dynamic tuning of cell and nuclear properties at different stages of migration is essential for maximizing migration efficiency. Our simulations also implicate confinement shape and confinement history as two important cell extrinsic regulators of cell invasiveness. Together, our findings illustrate the strength of a multicompartment model in dissecting the contributions of multiple factors that collectively influence confined cell migration.