Modeling Multi-Cellular Dynamics Regulated by ECM-Mediated Mechanical Communication via Active Particles with Polarized Effective Attraction

Abstract

Collective cell migration is crucial to many physiological and pathological processes. Recent experimental studies have indicated that the active traction forces generated by migrating cells in fibrous extracellular matrix (ECM) can mechanically remodel the ECM, enabling long-range propagation of cellular forces and leading to correlated migration dynamics regulated by the mechanical communication among the cells. Motivated by these experimental discoveries, we develop an active-particle model with polarized effective attractions (APPA) for modeling emergent multi-cellular migration dynamics regulated by ECM-mediated mechanical communications. Active particles with polarized pairwise attractions exhibit enhanced aggregation behaviors compared to classic active Brownian particles, especially at lower particle densities and larger rotational diffusivities. Importantly, in contrast to the classic ABP system, the high-density phase of APPA system exhibits strong dynamic correlation, which is characterized by the slowly decaying velocity correlation functions with a correlation length comparable to the linear size of high-density phase domain (i.e., cluster of the particles). The strongly correlated multi-cellular dynamics predicted by the APPA model are subsequently verified in {\it in vitro} experiments using MCF-10A cells. Our studies also indicate the importance of incorporating ECM-mediated mechanical coupling among the migrating cells for appropriately modeling emergent multi-cellular dynamics in complex micro-environments.