Cell Biophysics Laboratory, Optical Sciences Centre, Department of Physics and Astronomy, School of Science, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn VIC 3122, Australia.
Phys Biol. 2020 Jun 30;17(4):044001. doi: 10.1088/1478-3975/ab9242.
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 environment.
我们通过微流控系统研究了具有时变表皮生长因子浓度的 PC12 细胞的增殖情况。我们的测量结果显示，在三天的观察期内，细胞行为随频率而变化。根据施加的表皮生长因子的频率，细胞群体要么增加，要么减少，要么保持不变。作为生长因子频率函数的表观增殖率的图由 Fano 线形状公式数学描述。在线性响应理论的背景下，这些结果意味着 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。我们讨论了一个基于耦合振荡器周期性强迫的物理模型，该模型解释了这些观察结果。我们的结果和分析表明，通过控制细胞外环境的动力学，有可能影响细胞命运。
