Heltberg Mathias, von Borries Mads, Bendix Poul Martin, Oddershede Lene B, Jensen Mogens H
Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Front Cell Dev Biol. 2022 Jun 20;10:910738. doi: 10.3389/fcell.2022.910738. eCollection 2022.
The transcription factor NF-B plays a vital role in the control of the immune system, and following stimulation with TNF-α its nuclear concentration shows oscillatory behaviour. How environmental factors, in particular temperature, can control the oscillations and thereby affect gene stimulation is still remains to be resolved question. In this work, we reveal that the period of the oscillations decreases with increasing temperature. We investigate this using a mathematical model, and by applying results from statistical physics, we introduce temperature dependency to all rates, resulting in a remarkable correspondence between model and experiments. Our model predicts how temperature affects downstream protein production and find a crossover, where high affinity genes upregulates at high temperatures. Finally, we show how or that oscillatory temperatures can entrain NF-B oscillations and lead to chaotic dynamics presenting a simple path to chaotic conditions in cellular biology.
转录因子NF-κB在免疫系统的调控中起着至关重要的作用,在受到肿瘤坏死因子-α(TNF-α)刺激后,其核内浓度呈现出振荡行为。环境因素,特别是温度,如何控制这些振荡并进而影响基因刺激,仍是有待解决的问题。在这项工作中,我们揭示了振荡周期随温度升高而缩短。我们使用数学模型对此进行研究,并通过应用统计物理学的结果,将温度依赖性引入到所有速率中,从而使模型与实验结果呈现出显著的一致性。我们的模型预测了温度如何影响下游蛋白质的产生,并发现了一个交叉点,即在高温下高亲和力基因会上调。最后,我们展示了振荡温度如何能够锁定NF-κB振荡并导致混沌动力学,为细胞生物学中的混沌状态提供了一条简单途径。