Synergy of cell-cell repulsion and vacuolation in a computational model of lumen formation
Synergy of cell-cell repulsion and vacuolation in a computational model of lumen formation
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DOI：
10.1098/rsif.2013.1049
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发表时间：
2014-03-06
影响因子：
3.9
通讯作者：
Merks, Roeland M. H.
中科院分区：
文献类型：
--
作者：
Boas, Sonja E. M.;Merks, Roeland M. H.
血管发育（血管生成）的一个关键步骤是管腔形成：血管中空化以供血液灌注。两种替代的管腔形成机制，建议在不同类型的血管中发挥作用。空泡化机制被认为是通过细胞内空泡的合并在小血管中形成管腔，这一观点被扩展到通过空泡的胞吐作用形成细胞外管腔。细胞-细胞排斥机制是通过相邻细胞的主动排斥启动大血管细胞外腔的形成，并且主动的细胞形状变化扩展腔。我们使用了一个基于代理的计算机模型，基于细胞波茨模型，比较和研究这两种机制单独和组合。一个广泛的灵敏度分析表明，每个机制本身可以在一个狭窄的参数空间区域中产生管腔。然而，结合两种机制使得管腔形成对参数值更加稳健，这表明机制可以协同工作并并行操作，而不是在不同的血管类型中。
A key step in blood vessel development (angiogenesis) is lumen formation: the hollowing of vessels for blood perfusion. Two alternative lumen formation mechanisms are suggested to function in different types of blood vessels. The vacuolation mechanism is suggested for lumen formation in small vessels by coalescence of intracellular vacuoles, a view that was extended to extracellular lumen formation by exocytosis of vacuoles. The cell-cell repulsion mechanismis suggested to initiate extracellular lumen formation in large vessels by active repulsion of adjacent cells, and active cell shape changes extend the lumen. We used an agent-based computer model, based on the cellular Potts model, to compare and study both mechanisms separately and combined. An extensive sensitivity analysis shows that each of the mechanisms on its own can produce lumens in a narrow region of parameter space. However, combining both mechanisms makes lumen formation much more robust to the values of the parameters, suggesting that the mechanisms may work synergistically and operate in parallel, rather than in different vessel types.