Frank Anna S, Larripa Kamila, Ryu Hwayeon, Snodgrass Ryan G, Röblitz Susanna
Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway.
Department of Mathematics, Humboldt State University, Arcata, CA, USA.
J Theor Biol. 2021 Jan 21;509:110511. doi: 10.1016/j.jtbi.2020.110511. Epub 2020 Oct 9.
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.
在本文中，我们提出并分析了一个关于单个巨噬细胞极化的数学模型，该模型尽管简单，但在多稳定性方面表现出复杂的动力学特性。特别是，我们证明了调节机制和参数值中的不对称性对于观察多种表型很重要。分岔分析和敏感性分析表明，外部信号线索对于巨噬细胞定向分化并呈现某种表型是必要的，但巨噬细胞的内在信号通路同样重要。基于我们的数值结果，我们提出了一些假设，可通过实验室实验进一步研究，以加深我们对巨噬细胞极化的理解。
