Heltberg Mathias, Kellogg Ryan A, Krishna Sandeep, Tay Savaş, Jensen Mogens H
Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Biosystems Science and Engineering, ETH Zürich, 8092 Zürich, Switzerland.
Cell Syst. 2016 Dec 21;3(6):532-539.e3. doi: 10.1016/j.cels.2016.11.014.
Oscillations and noise drive many processes in biology, but how both affect the activity of the transcription factor nuclear factor κB (NF-κB) is not understood. Here, we observe that when NF-κB oscillations are entrained by periodic tumor necrosis factor (TNF) inputs in experiments, NF-κB exhibits jumps between frequency modes, a phenomenon we call "cellular mode-hopping." By comparing stochastic simulations of NF-κB oscillations to deterministic simulations conducted inside and outside the chaotic regime of parameter space, we show that noise facilitates mode-hopping in all regimes. However, when the deterministic system is driven by chaotic dynamics, hops between modes are erratic and short-lived, whereas in experiments, the system spends several periods in one entrainment mode before hopping and rarely visits more than two modes. The experimental behavior matches our simulations of noise-induced mode-hopping outside the chaotic regime. We suggest that mode-hopping is a mechanism by which different NF-κB-dependent genes under frequency control can be expressed at different times.
振荡和噪声驱动着生物学中的许多过程，但二者如何影响转录因子核因子κB（NF-κB）的活性尚不清楚。在此，我们观察到，在实验中当NF-κB振荡被周期性肿瘤坏死因子（TNF）输入所夹带时，NF-κB会在频率模式之间跳跃，我们将这一现象称为“细胞模式跳跃”。通过将NF-κB振荡的随机模拟与在参数空间混沌区域内外进行的确定性模拟相比较，我们表明噪声在所有区域都促进了模式跳跃。然而，当确定性系统由混沌动力学驱动时，模式之间的跳跃是不稳定且短暂的，而在实验中，系统在跳跃前会在一种夹带模式下停留几个周期，并且很少会访问超过两种模式。实验行为与我们在混沌区域之外对噪声诱导的模式跳跃的模拟相匹配。我们认为模式跳跃是一种机制，通过该机制，受频率控制的不同NF-κB依赖基因可以在不同时间表达。
