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体内三维环境中集体细胞迁移的建模与分析

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

作者信息

Cai Danfeng, Dai Wei, Prasad Mohit, Luo Junjie, Gov Nir S, Montell Denise J

机构信息

Molecular, Cellular and Developmental Biology, University of California Santa Barbara, CA 93106; Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD 21205;

Molecular, Cellular and Developmental Biology, University of California Santa Barbara, CA 93106;

出版信息

Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2134-41. doi: 10.1073/pnas.1522656113. Epub 2016 Mar 29.

Abstract

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.

摘要

在集体细胞迁移中,一个长期存在的问题是,相比于单个细胞迁移,形成细胞簇的相对优势可能是什么。集体迁移的细胞群规模的增加,是否能使它们在更大的距离上对化学梯度进行采样,因为细胞簇前后部之间的差异会大于单个细胞?我们将理论建模与实验相结合,以研究果蝇卵室中哺育细胞之间的边界细胞的集体迁移。我们发现,细胞簇大小与迁移速度呈正相关,直至某一特定点,超过该点速度就会骤降。这可能是由于周围哺育细胞产生的粘性阻力,以及所有细胞被限制在坚硬的细胞外基质中所致。该模型预测,在平面上移动的细胞,其簇大小与速度之间没有关系,这与在三维环境中的移动情况形成对比。我们的分析还表明,卵室中的整体趋化因子分布可能呈指数形式,在卵母细胞中浓度最高。这些发现通过将理论建模与实验相结合,为集体趋化作用提供了见解。

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Collective cell migration: guidance principles and hierarchies.集体细胞迁移:指导原则与层次结构。
Trends Cell Biol. 2015 Sep;25(9):556-66. doi: 10.1016/j.tcb.2015.06.003. Epub 2015 Jun 29.
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Cell migration: sinking in a gradient.细胞迁移:在梯度中下沉。
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