Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling
Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling
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DOI：
10.1016/j.celrep.2015.10.051
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发表时间：
2015-12-01
期刊：
影响因子：
8.8
通讯作者：
Kurihara, Hiroki
中科院分区：
文献类型：
--
作者：
Sugihara, Kei;Nishiyama, Koichi;Kurihara, Hiroki
血管生成是由形态发生细胞运动驱动的多细胞现象。我们最近报道形态发生的血管内皮细胞（EC）的行为是动态的和复杂的。然而，在血管生成形态发生中协调个体EC运动的主要机制在很大程度上仍然未知。在这里，我们提出了一个实验驱动的数学模型，使我们能够系统地剖析细胞机制，在分支伸长。我们发现，细胞自主和协调的行动支配这些多细胞的行为，和细胞自主的过程充分说明了在单细胞和细胞群体水平的形态发生EC动态的基本特征。通过改进我们的模型和实验验证，我们进一步确定了一个协调模式的尖端EC的行为，通过尖端和追随者EC之间的空间关系，这有利于尖端EC的向前运动。这些发现提供的见解，提高了我们的机械理解，不仅血管生成的形态发生，但也其他类型的多细胞现象。
Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon.