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A Mathematical Model of Collective Cell Migration in a Three-Dimensional Heterogeneous Environment

机译:三维异质环境中集体细胞迁移的数学模型

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摘要

Cell migration is essential in animal development, homeostasis, and disease progression, but many questions remain unanswered about how this process is controlled. While many kinds of individual cell movements have been characterized, less effort has been directed towards understanding how clusters of cells migrate collectively through heterogeneous, cellular environments. To explore this, we have focused on the migration of the border cells during Drosophila egg development. In this case, a cluster of different cell types coalesce and traverse as a group between large cells, called nurse cells, in the center of the egg chamber. We have developed a new model for this collective cell migration based on the forces of adhesion, repulsion, migration and stochastic fluctuation to generate the movement of discrete cells. We implement the model using Identical Math Cells, or IMCs. IMCs can each represent one biological cell of the system, or can be aggregated using increased adhesion forces to model the dynamics of larger biological cells. The domain of interest is filled with IMCs, each assigned specific biophysical properties to mimic a diversity of cell types. Using this system, we have successfully simulated the migration of the border cell cluster through an environment filled with larger cells, which represent nurse cells. Interestingly, our simulations suggest that the forces utilized in this model are sufficient to produce behaviors of the cluster that are observed in vivo, such as rotation. Our framework was developed to capture a heterogeneous cell population, and our implementation strategy allows for diverse, but precise, initial position specification over a three- dimensional domain. Therefore, we believe that this model will be useful for not only examining aspects of Drosophila oogenesis, but also for modeling other two or three-dimensional systems that have multiple cell types and where investigating the forces between cells is of interest.
机译:细胞迁移在动物发育,体内平衡和疾病进展中至关重要,但是有关如何控制该过程的许多问题仍未得到解答。尽管已表征了多种类型的单个细胞运动,但人们花了更少的精力来理解细胞簇如何通过异质细胞环境共同迁移。为了探索这一点,我们集中在果蝇卵发育过程中边界细胞的迁移。在这种情况下,不同类型细胞的簇会聚在一起并作为一个整体在卵室中央的大型细胞(称为护士细胞)之间穿越。我们已经基于粘附,排斥,迁移和随机波动的力为这种离散细胞的运动开发了一种新的集体细胞迁移模型。我们使用相同的数学单元或IMC实施模型。 IMC可以各自代表系统中的一个生物细胞,也可以使用增加的粘附力进行汇总以模拟较大生物细胞的动力学。感兴趣的域充满了IMC,每个IMC都分配了特定的生物物理特性以模仿多种细胞类型。使用该系统,我们成功地模拟了边界细胞簇在充满较大细胞(代表护士细胞)的环境中的迁移。有趣的是,我们的模拟表明,此模型中使用的力足以产生在体内观察到的簇的行为,例如旋转。开发我们的框架是为了捕获异类细胞群,并且我们的实施策略允许在三维域上进行多样化但精确的初始位置指定。因此,我们认为该模型不仅可用于检查果蝇卵子发生的方面,而且还可用于对具有多种细胞类型并且研究细胞间作用力的其他二维或三维系统进行建模。

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