Agent-based vs. equation-based multi-scale modeling for macrophage polarization.

ABSTRACT

Macrophages show high plasticity and result in heterogenic subpopulations or polarized states identified by specific cellular markers. These immune cells are typically characterized as pro-inflammatory, or classically activated M1, and anti-inflammatory, or alternatively activated M2. However, a more precise definition places them along a spectrum of activation where they may exhibit a number of pro- or anti-inflammatory roles. To understand M1-M2 dynamics in the context of a localized response and explore the results of different mathematical modeling approaches based on the same biology, we utilized two different modeling techniques, ordinary differential equation (ODE) modeling and agent-based modeling (ABM), to simulate the spectrum of macrophage activation to general pro- and anti-inflammatory stimuli on an individual and multi-cell level. The ODE model includes two hallmark pro- and anti-inflammatory signaling pathways and the ABM incorporates similar M1-M2 dynamics but in a spatio-temporal platform. Both models link molecular signaling with cellular-level dynamics. We then performed simulations with various initial conditions to replicate different experimental setups. Similar results were observed in both models after tuning to a common calibrating experiment. Comparing the two models' results sheds light on the important features of each modeling approach. When more data is available these features can be considered when choosing techniques to best fit the needs of the modeler and application.