Modular microenvironment components reproduce vascular dynamics de novo in a multi-scale agent-based model

Cells do not exist in isolation; they continuously act within and react to their environment. And this environment is not static; it continuously adapts and responds to cells. Here, we investigate how vascular structure and function impact emergent cell population behavior using an agent-based model (ABM). Our ABM enables researchers to "mix and match" cell agents, subcellular modules, and microenvironment components ranging from simple nutrient sources to complex, realistic vascular architectures that accurately capture hemodynamics. We use this ABM to highlight the bilateral relationship between cells and nearby vasculature, demonstrate the effect of vascular structure on environmental heterogeneity, and emphasize the non-linear, non-intuitive relationship between vascular function and the behavior of cell populations over time. Our ABM is well suited to characterizing in vitro and in vivo studies, with applications from basic science to translational synthetic biology and medicine. The model is freely available at https://github.com/bagherilab/ARCADE. A record of this paper's transparent peer review process is included in the supplemental information.