Composite cell agent model of epithelial culture in vitro

An advantage of the synthetic, agent-oriented modeling approach is the ease with which model components can be refined or replaced with additional mechanisms and details. Here we present an agent-based model of epithelial cell culture, and describe revisions made to include subcellular details. Specifically, we developed new components inside cell agents, thereby evolving atomic cell agents into composite counterparts. The new components mapped abstractly to subcellular features involved in cell surface differentiation, which replaced agent rules governing simulated cell polarization and depolarization. Cross-model validation results under normal conditions confirmed that the revisions did not measurably alter model phenotype, specifically the simulated growth dynamics and gross morphology. However, cross-model validation results uncovered discrepancies for dysregulated conditions where one or more cell agent actions (e.g., division and death) were blocked in a probabilistic manner. Their elimination required reengineering the composite. We expect the approach and methods developed will facilitate and accelerate knowledge discovery in biomedical research.