Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN, USA.
Department of Mathematics and Statistics, University of Maryland Baltimore County, Baltimore, MD, USA.
Bull Math Biol. 2019 May;81(5):1268-1302. doi: 10.1007/s11538-019-00573-5. Epub 2019 Feb 12.
Oscillations occur in a wide variety of essential cellular processes, such as cell cycle progression, circadian clocks and calcium signaling in response to stimuli. It remains unclear how intrinsic stochasticity can influence these oscillatory systems. Here, we focus on oscillations of Cdc42 GTPase in fission yeast. We extend our previous deterministic model by Xu and Jilkine to construct a stochastic model, focusing on the fast diffusion case. We use SSA (Gillespie's algorithm) to numerically explore the low copy number regime in this model, and use analytical techniques to study the long-time behavior of the stochastic model and compare it to the equilibria of its deterministic counterpart. Numerical solutions suggest noisy limit cycles exist in the parameter regime in which the deterministic system converges to a stable limit cycle, and quasi-cycles exist in the parameter regime where the deterministic model has a damped oscillation. Near an infinite period bifurcation point, the deterministic model has a sustained oscillation, while stochastic trajectories start with an oscillatory mode and tend to approach deterministic steady states. In the low copy number regime, metastable transitions from oscillatory to steady behavior occur in the stochastic model. Our work contributes to the understanding of how stochastic chemical kinetics can affect a finite-dimensional dynamical system, and destabilize a deterministic steady state leading to oscillations.
在各种基本的细胞过程中都会发生波动,例如细胞周期进展、生物钟和钙信号对刺激的反应。目前尚不清楚内源性随机性如何影响这些振荡系统。在这里,我们专注于裂殖酵母中 Cdc42 GTPase 的波动。我们通过 Xu 和 Jilkine 扩展了以前的确定性模型,构建了一个专注于快速扩散情况的随机模型。我们使用 SSA(Gillespie 算法)在该模型中数值探索低拷贝数的情况,并使用分析技术研究随机模型的长时间行为,并将其与确定性模型的平衡点进行比较。数值解表明,在确定性系统收敛到稳定极限环的参数范围内存在噪声极限环,在确定性模型具有阻尼振荡的参数范围内存在准周期。在无限周期分岔点附近,确定性模型具有持续的振荡,而随机轨迹开始时处于振荡模式,并趋于接近确定性稳定状态。在低拷贝数范围内,随机模型中会发生从振荡到稳定行为的亚稳态转变。我们的工作有助于理解随机化学动力学如何影响有限维动力系统,并使确定性稳定状态失稳导致振荡。