A multicellular organization is a complex resulting from the coordinated migration of cells to form a specific pattern. The directionality of migration is governed by the mechanical and molecular dynamics of factors secreted from the cells. The mechanism underlying pattern formation is too complex to unveil by culture experiments alone. A mathematical model could provide a powerful tool for elucidating the mechanism of pattern formation by computing the molecular dynamics, which are difficult to visualize by culture experiments. However, there tends to be a gap between mathematical models and experimental research due to incongruity between the idealized conditions of the model and the experimental results. This paper presents an in vitro-in silico interface platform for elucidating the logic of multicellular pattern formation. Two-dimensional collective cell pattern formation was developed using normal human bronchial epithelial cells. Then, geometrical control of collective cells followed by feedback iteration was used to bridge the gap between the mathematical model and in vitro experiments. The mechanisms underlying the pattern formation of bronchial epithelial cells were evaluated using a reaction-diffusion model. The results indicated that differences in the diffusion rates of the activator and inhibitor determine the direction of collective cell migration to form a specific pattern.

中文翻译：

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一个体外-计算机界面平台，用于时空分析集体上皮细胞中的图案形成。

多细胞组织是由细胞协调迁移形成特定模式而形成的复杂结构。迁移的方向性由细胞分泌的因子的机械和分子动力学决定。模式形成的机制太复杂，无法仅通过培养实验来揭示。数学模型可以提供一个强大的工具，通过计算分子动力学来阐明模式形成的机理，而分子动力学很难通过培养实验将其可视化。但是，由于模型的理想条件与实验结果之间的不一致，因此数学模型与实验研究之间往往存在差距。本文提出了一种体外-计算机接口平台，以阐明多细胞模式形成的逻辑。使用正常人支气管上皮细胞发展了二维集体细胞模式的形成。然后，对集体细胞进行几何控制，然后进行反馈迭代，以弥合数学模型与体外实验之间的差距。使用反应扩散模型评估支气管上皮细胞模式形成的基础机制。结果表明，活化剂和抑制剂扩散速率的差异决定了集体细胞迁移形成特定模式的方向。使用反应扩散模型评估支气管上皮细胞模式形成的基础机制。结果表明，活化剂和抑制剂扩散速率的差异决定了集体细胞迁移形成特定模式的方向。使用反应扩散模型评估支气管上皮细胞模式形成的基础机制。结果表明，活化剂和抑制剂扩散速率的差异决定了集体细胞迁移形成特定模式的方向。