Phenotype switching in a global method for agent-based models of biological tissue.

Agent-based models (ABMs) are an increasingly important tool for understanding the complexities presented by phenotypic and spatial heterogeneity in biological tissue. The resolution a modeler can achieve in these regards is unrivaled by other approaches. However, this comes at a steep computational cost limiting either the scale of such models or the ability to explore, parameterize, analyze, and apply them. When the models involve molecular-level dynamics, especially cell-specific dynamics, the limitations are compounded. We have developed a global method for solving these computationally expensive dynamics significantly decreases the computational time without altering the behavior of the system. Here, we extend this method to the case where cells can switch phenotypes in response to signals in the microenvironment. We find that the global method in this context preserves the temporal population dynamics and the spatial arrangements of the cells while requiring markedly less simulation time. We thus add a tool for efficiently simulating ABMs that captures key facets of the molecular and cellular dynamics in heterogeneous tissue.