We examined PC12 cell proliferation in environments with temporally varying epidermal growth factor concentrations by means of a microfluidic system. Our measurements revealed frequency-dependent cell behaviour over an observation period of three days. The cell population either increased, decreased or remained constant depending on the frequency of epidermal growth factor applied. A plot of the apparent proliferation rate as a function of growth-factor frequency was mathematically described by the Fano line-shape formula. In the context of linear response theory, these results imply that the PC12 cells compute zero, first and second-order time derivatives of the ligand concentration and utilise this information to decide to proliferate or die. We discuss a physical model based on periodic forcing of coupled oscillators that accounts for these observations. Our results and analysis suggest the possibility to influence cell fate by controlling the dynamics of the extracellular en...

中文翻译：

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频率依赖性细胞增殖是否表现出Fano型共振？

我们通过微流体系统在表皮生长因子浓度随时间变化的环境中检查了PC12细胞的增殖。我们的测量揭示了三天观察期内频率依赖性的细胞行为。细胞数量根据表皮生长因子的频率增加，减少或保持恒定。表观增殖率与生长因子频率的函数关系图通过Fano线形公式进行了数学描述。在线性响应理论的背景下，这些结果暗示PC12细胞计算配体浓度的零，一阶和二阶时间导数，并利用此信息来决定增殖或死亡。我们讨论了基于耦合振荡器的周期性强迫的物理模型，这些物理模型解释了这些观察结果。我们的结果和分析表明，通过控制细胞外细胞的动力学来影响细胞命运的可能性。