Image based validation of dynamical models for cell reorientation.
Image based validation of dynamical models for cell reorientation.
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DOI：
10.1002/cyto.a.22600
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Bretschneider T
中科院分区：
文献类型：
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作者：
Lockley R;Ladds G;Bretschneider T
定向细胞运动的一个关键特征是细胞响应细胞外刺激方向的变化而快速重新定向的能力。数学模型提出了完全不同的调节机制来解释重新定位，这就提出了我们如何以严格的方式验证这些模型的问题。在这项研究中，我们拟合三个反应扩散模型的实验数据Dictyosteomaamoeastrum重定向响应于交替梯度的机械剪切流。我们用来拟合的实验读数是皮质F-肌动蛋白标记细胞前沿的荧光报告分子的时空分布。同时拟合在不同条件下进行的实验，以挑战具有不同类型的细胞动力学的模型。虽然Otsuji提出的模型无法提供令人满意的拟合，但Meinhardt和Levchenko提出的模型同样拟合得很好。此外，我们表明，减少三个变量的Meinhardt模型的两个变量的模型也提供了一个很好的拟合，但具有的所有参数是唯一可识别的优点。我们的工作表明，模型选择和可识别性分析，通常适用于系统生物学中的时间动力学问题，可以是一个强大的工具时，扩展到时空成像数据。
A key feature of directed cell movement is the ability of cells to reorient quickly in response to changes in the direction of an extracellular stimulus. Mathematical models have suggested quite different regulatory mechanisms to explain reorientation, raising the question of how we can validate these models in a rigorous way. In this study, we fit three reaction—diffusion models to experimental data of Dictyostelium amoebae reorienting in response to alternating gradients of mechanical shear flow. The experimental readouts we use to fit are spatio-temporal distributions of a fluorescent reporter for cortical F-actin labeling the cell front. Experiments performed under different conditions are fitted simultaneously to challenge the models with different types of cellular dynamics. Although the model proposed by Otsuji is unable to provide a satisfactory fit, those suggested by Meinhardt and Levchenko fit equally well. Further, we show that reduction of the three-variable Meinhardt model to a two-variable model also provides an excellent fit, but has the advantage of all parameters being uniquely identifiable. Our work demonstrates that model selection and identifiability analysis, commonly applied to temporal dynamics problems in systems biology, can be a powerful tool when extended to spatio-temporal imaging data.