Bifurcation analysis reveals mechanisms of macrophage polarization

Macrophages polarize to spectrum of phenotypes in order to mediate tissue regeneration. New therapeutic approaches tend to target macrophage polarization and modify their phenotypes to alter tissue destiny (Sica et al. ۲۰۱۲). Revealing polarization mechanisms in macrophages paves the way to develop potential therapeutics. Here, a nonlinear model is proposed for macrophage and polarization mechanisms are studied using bifurcation analysis. IL۴, IFNγ and LPS are selected as bifurcation parameters and possible steady states of STAT۱, STAT۶, and NFκB mediators are revealed. Saddle-node bifurcations are detected in macrophage dynamics resulting in different combinations of steady states of said mediators which we attribute to different phenotypes. We detected only ۹ stable phenotypes rather than a spectrum by analyzing the proposed macrophage model. The polarization model as well as our results is validated against experimental data and dynamic bifurcation is recognized as a vital mechanism in macrophage polarization.

Keywords:

Bifurcation Analysis , Macrophage Polarization , Non-linear Mathematical model , Phenotype Selection