Cancer Cell Dynamics Navigating Complex Microenvironment: Active Nematics and Dynamic Heterogeneity

Abstract

Growing evidence indicates that the motility of multicellular systems exhibits active nematic characteristics. However, the impact of cell-to-cell variability, particularly the relationship between a cell’s dynamic phenotype and its contribution to nematic order, remains poorly understood. Here, we examine the motility of monolayers of micropatterned breast cancer cells and observe the emergence of robust nematic order that evolves spatiotemporally, despite the absence of coherent tissue flow. We identify a distinct subpopulation of cells, termed ``patrollers'', which display strongly polarized migration and appear to reinforce local nematic alignment. To elucidate the underlying mechanisms, we develop a mean-field theoretical model that captures the essential contributions of this subpopulation and yields predictions consistent with our experimental observations. Our results indicate that nematic order within multicellular systems may be driven not by uniform behavior across the entire population, but rather by the dominant influence of a specialized subset of cells that orchestrate collective alignment.