Mathematical Analysis of the Escherichia coli Chemotaxis Signalling Pathway.

Mathematical Analysis of the Escherichia coli Chemotaxis Signalling Pathway.
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DOI:
10.1007/s11538-018-0400-z
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发表时间:
2018-04
影响因子:
3.5
通讯作者:
Tindall MJ
Tindall MJ
中科院分区:
数学4区
文献类型:
--
作者:
Edgington MP;Tindall MJ

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我们进行了详细的数学分析,最近的非线性常微分方程(ODE)模型描述的大肠杆菌细胞内的趋化信号级联。该模型包括细胞信号级联的详细描述和受体活性的平均近似。稳态稳定性分析表明,该系统具有一个正的真实的稳态是渐近稳定的。鉴于磷酸化切布(CheB-P)和受体状态之间的负反馈的发生,我们问在什么条件下,系统可能会表现出类似的行为。参数空间的详细分析表明,虽然在已知的生物限制内的动力学速率参数的变化是不可能导致这种行为,在总浓度的信号蛋白的变化。我们假设,实验观察到的过冲行为实际上可以通过阻尼振荡动力学来描述,并考虑过冲幅度,总细胞蛋白质浓度和外部配体刺激的大小之间的关系。完整ODE模型中的模型简化使我们能够理解磷酸化事件与CheB-P和受体甲基化之间的负反馈之间的联系,以及阐明为什么一些数学模型表现出过冲而另一些则没有。我们的论文结束时,讨论细胞间的总蛋白浓度的变异性,作为一种手段,确保人口的总体生存细胞受到不同的环境。
We undertake a detailed mathematical analysis of a recent nonlinear ordinary differential equation (ODE) model describing the chemotactic signalling cascade within an Escherichia coli cell. The model includes a detailed description of the cell signalling cascade and an average approximation of the receptor activity. A steady-state stability analysis reveals the system exhibits one positive real steady state which is shown to be asymptotically stable. Given the occurrence of a negative feedback between phosphorylated CheB (CheB-P) and the receptor state, we ask under what conditions the system may exhibit oscillatory-type behaviour. A detailed analysis of parameter space reveals that whilst variation in kinetic rate parameters within known biological limits is unlikely to lead to such behaviour, changes in the total concentration of the signalling proteins do. We postulate that experimentally observed overshoot behaviour can actually be described by damped oscillatory dynamics and consider the relationship between overshoot amplitude, total cell protein concentration and the magnitude of the external ligand stimulus. Model reductions in the full ODE model allow us to understand the link between phosphorylation events and the negative feedback between CheB-P and receptor methylation, as well as elucidate why some mathematical models exhibit overshoot and others do not. Our paper closes by discussing intercell variability of total protein concentration as a means of ensuring the overall survival of a population as cells are subjected to different environments.
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