Prescott Thomas P, Zhu Kan, Zhao Min, Baker Ruth E
Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford, United Kingdom; Alan Turing Institute, London, United Kingdom.
Department of Ophthalmology and Vision Science, Department of Dermatology, Institute for Regenerative Cures, University of California, Sacramento, California.
Biophys J. 2021 Aug 17;120(16):3363-3373. doi: 10.1016/j.bpj.2021.06.034. Epub 2021 Jul 7.
Cell motility in response to environmental cues forms the basis of many developmental processes in multicellular organisms. One such environmental cue is an electric field (EF), which induces a form of motility known as electrotaxis. Electrotaxis has evolved in a number of cell types to guide wound healing and has been associated with different cellular processes, suggesting that observed electrotactic behavior is likely a combination of multiple distinct effects arising from the presence of an EF. To determine the different mechanisms by which observed electrotactic behavior emerges, and thus to design EFs that can be applied to direct and control electrotaxis, researchers require accurate quantitative predictions of cellular responses to externally applied fields. Here, we use mathematical modeling to formulate and parameterize a variety of hypothetical descriptions of how cell motility may change in response to an EF. We calibrate our model to observed data using synthetic likelihoods and Bayesian sequential learning techniques and demonstrate that EFs bias cellular motility through only one of a selection of hypothetical mechanisms. We also demonstrate how the model allows us to make predictions about cellular motility under different EFs. The resulting model and calibration methodology will thus form the basis for future data-driven and model-based feedback control strategies based on electric actuation.
细胞对环境线索做出反应的运动性构成了多细胞生物许多发育过程的基础。一种这样的环境线索是电场(EF),它会诱导一种被称为电趋性的运动形式。电趋性在多种细胞类型中进化出来以指导伤口愈合,并且与不同的细胞过程相关联,这表明观察到的电趋性行为可能是由电场存在所产生的多种不同效应的组合。为了确定观察到的电趋性行为出现的不同机制,从而设计可用于引导和控制电趋性的电场,研究人员需要对细胞对外加电场的反应进行准确的定量预测。在这里,我们使用数学建模来制定和参数化关于细胞运动性如何响应电场而变化的各种假设描述。我们使用合成似然性和贝叶斯序贯学习技术将我们的模型校准到观察数据,并证明电场仅通过一系列假设机制中的一种来使细胞运动性产生偏差。我们还展示了该模型如何使我们能够对不同电场下的细胞运动性进行预测。因此,所得的模型和校准方法将为未来基于电驱动的数据驱动和基于模型的反馈控制策略奠定基础。