Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

Modeling and analysis of collective cell migration in an in vivo three-dimensional environment
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DOI:
10.1073/pnas.1522656113
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发表时间:
2016-04-12
影响因子:
11.1
通讯作者:
Montell, Denise J.
Montell, Denise J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cai, Danfeng;Dai, Wei;Montell, Denise J.

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在集体细胞迁移中,一个长期存在的问题是,形成一个集群比单独迁移有什么相对优势。一个集体迁移的细胞群的大小的增加是否使它们能够在更大的距离上采样化学梯度,因为集群前后之间的差异将大于单个细胞?我们将理论模型与实验相结合,研究了果蝇卵室中乳细胞之间的边界细胞的集体迁移。我们发现集群大小与迁移速度正相关,直到迁移速度下降的特定点。这可能是由于来自周围护理细胞的粘性阻力的影响,以及所有细胞被限制在坚硬的细胞外基质中。该模型预测在平面上移动的细胞簇大小和速度之间没有关系,与在3D环境中的移动相反。我们的分析还表明,卵腔内的总体化学引诱剂可能呈指数型,卵母细胞中的浓度最高。这些发现通过将理论建模与实验相结合,为集体趋化性提供了见解。
A long-standing question in collective cell migration has been what might be the relative advantage of forming a cluster over migrating individually. Does an increase in the size of a collectively migrating group of cells enable them to sample the chemical gradient over a greater distance because the difference between front and rear of a cluster would be greater than for single cells? We combined theoretical modeling with experiments to study collective migration of the border cells in-between nurse cells in the Drosophila egg chamber. We discovered that cluster size is positively correlated with migration speed, up to a particular point above which speed plummets. This may be due to the effect of viscous drag from surrounding nurse cells together with confinement of all of the cells within a stiff extracellular matrix. The model predicts no relationship between cluster size and velocity for cells moving on a flat surface, in contrast to movement within a 3D environment. Our analyses also suggest that the overall chemoattractant profile in the egg chamber is likely to be exponential, with the highest concentration in the oocyte. These findings provide insights into collective chemotaxis by combining theoretical modeling with experimentation.