Double-strand break-induced (DSB) cells send signal that induces DSBs in neighbour cells, resulting in the interaction among cells sharing the same medium. Since p53 network gives oscillatory response to DSBs, such interaction among cells could be modelled as an excitatory coupling of p53 network oscillators. This study proposes a plausible coupling model of three-mode two-dimensional oscillators, which models the p53-mediated cell fate selection in globally coupled DSB-induced cells. The coupled model consists of ATM and Wip1 proteins as variables. The coupling mechanism is realised through ATM variable via a mean-field modelling the bystander signal in the intercellular medium. Investigation of the model reveals that the coupling generates more sensitive DNA damage response by affecting cell fate selection. Additionally, the authors search for the cause-effect relationship between coupled p53 network oscillators and bystander effect (BE) endpoints. For this, they search for the possible values of uncertain parameters that may replicate BE experiments' results. At certain parametric regions, there is a correlation between the outcomes of cell fate and endpoints of BE, suggesting that the intercellular coupling of p53 network may manifest itself as the form of observed BEs.

中文翻译：

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细胞命运选择模型的耦合增强了 DNA 损伤反应，可能是 BE 现象的基础。

双链断裂诱导 (DSB) 细胞发出信号，诱导相邻细胞中的 DSB，从而导致共享相同介质的细胞之间发生相互作用。由于 p53 网络对 DSB 产生振荡反应，因此细胞之间的这种相互作用可以建模为 p53 网络振荡器的兴奋性耦合。这项研究提出了一种三模二维振荡器的合理耦合模型，该模型模拟了全局耦合 DSB 诱导细胞中 p53 介导的细胞命运选择。耦合模型由 ATM 和 Wip1 蛋白作为变量组成。耦合机制是通过 ATM 变量通过对细胞间介质中的旁观者信号进行平均场建模来实现的。对模型的研究表明，耦合通过影响细胞命运选择而产生更敏感的 DNA 损伤反应。此外，作者还寻找耦合 p53 网络振荡器和旁观者效应 (BE) 端点之间的因果关系。为此，他们寻找可能复制 BE 实验结果的不确定参数的可能值。在某些参数区域，细胞命运的结果与 BE 终点之间存在相关性，这表明 p53 网络的细胞间耦合可能表现为观察到的 BE 的形式。