Bifurcation and sensitivity analysis reveal key drivers of multistability in a model of macrophage polarization

JOURNAL OF THEORETICAL BIOLOGY

卷:509

Article

Frank, Anna S.¹  Larripa, Kamila²  Ryu, Hwayeon³  Snodgrass, Ryan G.⁴  Roeblitz, Susanna¹ 

[1] Univ Bergen, Dept Informat, Computat Biol Unit, Bergen, Norway

[2] Humboldt State Univ, Dept Math, Arcata, CA 95521 USA

[3] Elon Univ, Dept Math & Stat, Elon, NC USA

[4] Goethe Univ, Inst Biochem, Frankfurt, Germany

关键词: Dynamical Systems;    Steady States;    Cellular Signaling;    Phenotypes;   

DOI  :  10.1016/j.jtbi.2020.110511

来源: Elsevier

【 摘 要 】

In this paper, we present and analyze a mathematical model for polarization of a single macrophage which, despite its simplicity, exhibits complex dynamics in terms of multistability. In particular, we demonstrate that an asymmetry in the regulatory mechanisms and parameter values is important for observing multiple phenotypes. Bifurcation and sensitivity analyses show that external signaling cues are necessary for macrophage commitment and emergence to a phenotype, but that the intrinsic macrophage pathways are equally important. Based on our numerical results, we formulate hypotheses that could be further investigated by laboratory experiments to deepen our understanding of macrophage polarization. (C) 2020 The Author(s). Published by Elsevier Ltd.

【 授权许可】

Free