Geometry of disordered porous environments regulates cell migration

Cell migration is a dynamic process that is of critical importance to various aspects of living organisms, including organogenesis, wound healing, and immune responses. Several external factors are known to influence and direct active cell movement, such as chemokine gradients and the composition and mechanical properties of the extracellular matrix (ECM). While progress has been made in elucidating some of the biochemical pathways that control cell migration, little is known about the impact of the porous structure of the ECM on active cell motion. Here, by combining computational modeling and theory, we reveal how porous environments, as represented by the ECM, determine cell migration dynamics. Simulating cell movement in a 3D cellular Potts model accounting for amoeboid-like cell shape dynamics, we show that cell migration within disordered porous environments is characterized by distinct transient motility regimes that deviate from persistent motion and are best described by the 'hopping' of cells between 'traps.' Using theory, we can show how these motility regimes and large-scale transport properties are linked to geometrical properties of the microstructure. Importantly, our analyses reveal that spatial heterogeneities in the porosity lead to nonhomogeneous cell distributions and effectively guide cell movement toward regions of low porosity, an effect which we term as porotaxis. Overall, our work reveals the porosity of the ECM as an important control parameter that shapes cell migration and cellular distribution, and provides a conceptual framework to relate experimentally observed cell motility modes to tissue structures and vice versa. This connection between geometry and cell motility could enhance our understanding of how structural elements shape cell migration and tissue organization in various conditions, such as chronic inflammation, immunity, and cancer.