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Cell-based simulations of biased epithelial lung growth.
Physical Biology ( IF 2.0 ) Pub Date : 2019-12-13 , DOI: 10.1088/1478-3975/ab5613
Anna Stopka 1 , Marco Kokic , Dagmar Iber
Affiliation  

During morphogenesis, epithelial tubes elongate. In the case of the mammalian lung, biased elongation has been linked to a bias in cell shape and cell division, but it has remained unclear whether a bias in cell shape along the axis of outgrowth is sufficient for biased outgrowth and how it arises. Here, we use our 2D cell-based tissue simulation software [Formula: see text] to investigate the conditions for biased epithelial outgrowth. We show that the observed bias in cell shape and cell division can result in the observed bias in outgrowth only in the case of strong cortical tension, and comparison to biological data suggests that the cortical tension in epithelia is likely sufficient. We explore mechanisms that may result in the observed bias in cell division and cell shapes. To this end, we test the possibility that the surrounding tissue or extracellular matrix acts as a mechanical constraint that biases growth in the longitudinal direction. While external compressive forces can result in the observed bias in outgrowth, we find that they do not result in the observed bias in cell shapes. We conclude that other mechanisms must exist that generate the bias in lung epithelial outgrowth.

中文翻译:

基于细胞的模拟上皮肺生长。

在形态发生过程中,上皮管会伸长。就哺乳动物的肺而言,偏向的伸长与细胞形状和细胞分裂的偏向有关,但尚不清楚沿向外生长轴的细胞形状偏向是否足以用于偏向的生长及其如何产生。在这里,我们使用基于2D细胞的组织模拟软件[公式:参见文本]研究上皮细胞偏向生长的条件。我们显示,仅在强皮质张力的情况下,观察到的细胞形状和细胞分裂的偏见才能导致所观察到的向外生长的偏见,并且与生物学数据的比较表明,上皮中的皮质张力很可能是足够的。我们探讨了可能导致观察到的细胞分裂和细胞形状偏差的机制。为此,我们测试了周围组织或细胞外基质充当机械约束的可能性,该机械约束使纵向生长偏向。虽然外部压缩力会导致观察到的生长偏差,但我们发现它们不会导致观察到的细胞形状偏差。我们得出的结论是,还必须存在其他机制,这些机制会导致肺上皮细胞过度生长。
更新日期:2019-11-01
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