Impacts of communication length-scale on cellular invasion of tumor stroma using a novel ECM model

Understanding long-range cellular migration is key to an understanding of cancer metastasis as well as other biological processes such as embryogenesis and formation of tissue morphology. Due to constraints on cellular and tissue level imaging, gaining that understanding as it emerges from cell-cell and cell-environmental interactions is challenging. To aid in gaining that understanding with respect to the physical environment, we developed a novel mathematical extracellular matrix (ECM) model capturing three components of ECM: fiber orientation, alignment, and density. This model is notable in its stripping down the ECM to its most essential components. We implemented this model in PhysiCell, a cell-based modeling framework, thus allowing coupling between it and cell-agents. We then explored rules of interactions between cells, their physical environment (the ECM), and the diffusive chemical environment. We observed that locally sensed, long range (on the order of a few cell diameters) physical signals communicated via ECM remodeling alter the dynamics of cellular invasion, producing new results. Comparing these results to simulations lacking long-range permanently written signals, we see more cellular trafficking and movement. This advance brings us one step closer to understanding processes of collective cellular migration and closer to understanding the initial steps of cancer metastasis.