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A Model of Cell Biological Signaling Predicts a Phase Transition of Signaling and Provides Mathematical Formulae

机译:细胞生物学信号传导模型可预测信号传导的相变并提供数学公式

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摘要

A biological signal is transmitted by interactions between signaling molecules in the cell. To date, there have been extensive studies regarding signaling pathways using numerical simulation of kinetic equations that are based on equations of continuity and Fick’s law. To obtain a mathematical formulation of cell signaling, we propose a stability kinetic model of cell biological signaling of a simple two-parameter model based on the kinetics of the diffusion-limiting step. In the present model, the signaling is regulated by the binding of a cofactor, such as ATP. Non-linearity of the kinetics is given by the diffusion fluctuation in the interaction between signaling molecules, which is different from previous works that hypothesized autocatalytic reactions. Numerical simulations showed the presence of a critical concentration of the cofactor beyond which the cell signaling molecule concentration is altered in a chaos-like oscillation with frequency, which is similar to a discontinuous phase transition in physics. Notably, we found that the frequency is given by the logarithm function of the difference of the outside cofactor concentration from the critical concentration. This implies that the outside alteration of the cofactor concentration is transformed into the oscillatory alteration of cell inner signaling. Further, mathematical stability kinetic analysis predicted a discontinuous dynamic phase transition in the critical state at which the cofactor concentration is equivalent to the critical concentration. In conclusion, the present model illustrates a unique feature of cell signaling, and the stability analysis may provide an analytical framework of the cell signaling system and a novel formulation of biological signaling.
机译:生物信号通过细胞中信号分子之间的相互作用而传递。迄今为止,已经使用基于连续性方程和菲克定律的动力学方程式的数值模拟对信号通路进行了广泛的研究。为了获得细胞信号传导的数学公式,我们基于扩散限制步骤的动力学,提出了一个简单的两参数模型的细胞生物信号传导的稳定动力学模型。在本模型中,信号传导受辅因子例如ATP的结合调节。动力学的非线性是由信号分子之间相互作用中的扩散波动引起的,这与先前的假设自催化反应的工作不同。数值模拟显示了辅因子的临界浓度的存在,超过该浓度时,细胞信号分子的浓度会随着频率的混沌变化而改变,这类似于物理学中的不连续相变。值得注意的是,我们发现频率是由外部辅因子浓度与临界浓度之差的对数函数给出的。这意味着辅因子浓度的外部改变被转化为细胞内部信号传导的振荡改变。此外,数学稳定性动力学分析预测了在临界状态下不连续的动态相变,在该状态下辅因子浓度等于临界浓度。总之,本模型说明了细胞信号传导的独特特征,并且稳定性分析可以提供细胞信号传导系统的分析框架和生物信号传导的新形式。

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    Tatsuaki Tsuruyama;

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  • 年(卷),期 -1(9),7
  • 年度 -1
  • 页码 e102911
  • 总页数 8
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