Avalanches during epithelial tissue growth; Uniform Growth and a drosophila eye disc model.
Avalanches during epithelial tissue growth; Uniform Growth and a drosophila eye disc model.
复制标题
DOI：
10.1371/journal.pcbi.1009952
复制
发表时间：
2022-03
影响因子：
4.3
通讯作者：
Haas S
中科院分区：
文献类型：
--
作者：
Courcoubetis G;Xu C;Nuzhdin SV;Haas S
上皮组织构成了一种特殊类型的活性物质，具有让人想起无定形材料的非线性性质。在准静态顶点模型所模拟的增殖上皮的背景下，我们识别了新的离散组织尺度重排，即细胞重排雪崩，这是集体细胞运动的一种形式。在雪崩期间，绝大多数细胞保留了它们的邻居，由此产生的细胞轨迹在外围是放射状的，在核心是一个漩涡。在这些雪崩发生后，上皮区不连续地生长。雪崩被发现是随机的，其强度与组织中细胞的密度相关。总体而言，雪崩沿着组织重新分配累积的局部空间压力。此外，雪崩强度的分布服从幂定律，其指数与非晶态材料中的纯粹雪崩一致。为了了解雪崩在器官发育中的作用，我们使用一个包括化学和机械信号的计算模型模拟了三龄果蝇眼盘的上皮生长。在3龄时，形态发生沟(Mf)--一个10个细胞宽的顶区收缩波--通过上皮传播。这些模拟被用来了解生长过程的细节，MF对组织尺度上的生长动力学的影响，并为实验观察做出预测。研究发现，雪崩取决于中膜细胞顶端收缩的强度，更强的顶端收缩导致更少的频率和更明显的雪崩。本文的结果强调了模拟的组织生长动力学对松弛时间的依赖性，并为体外实验提供了指导。上皮组织具有有趣的特性。它们通常被描述为粘弹性材料，在短时间尺度上表现为弹性固体，在长时间尺度上表现为液体。当组织增殖时，细胞分裂需要细胞重新排列并相互移位。为了缓解增殖压力，细胞配备了机械设备，使它们能够对机械信号做出反应并重新排列。在此，我们在顶点模型的基础上进行计算模拟，以研究上皮生长。在我们的模拟中，当组织大小达到数千个细胞时，我们观察到随机阶梯状生长间断的流行。这些新发现的事件，我们称之为雪崩，涉及组织中所有细胞的集体重排，它们伴随着局部的细胞压力重分布和细胞的集体净径向位移。我们在空间均匀和时间无关的生长模型的简单设置下，以及在实验校准的果蝇眼盘生长模型的背景下，研究它们的性质。利用眼盘生长模型，我们还研究了局部细胞机械变形与全球生长动力学之间的关系。我们得出结论，当局部突起不足时，雪崩构成了上皮组织释放累积的增殖应力的宏观途径。
Epithelial tissues constitute an exotic type of active matter with non-linear properties reminiscent of amorphous materials. In the context of a proliferating epithelium, modeled by the quasistatic vertex model, we identify novel discrete tissue scale rearrangements, i.e. cellular rearrangement avalanches, which are a form of collective cell movement. During the avalanches, the vast majority of cells retain their neighbors, and the resulting cellular trajectories are radial in the periphery, a vortex in the core. After the onset of these avalanches, the epithelial area grows discontinuously. The avalanches are found to be stochastic, and their strength is correlated with the density of cells in the tissue. Overall, avalanches redistribute accumulated local spatial pressure along the tissue. Furthermore, the distribution of avalanche magnitudes is found to obey a power law, with an exponent consistent with sheer induced avalanches in amorphous materials. To understand the role of avalanches in organ development, we simulate epithelial growth of the Drosophila eye disc during the third instar using a computational model, which includes both chemical and mechanistic signaling. During the third instar, the morphogenetic furrow (MF), a ~10 cell wide wave of apical area constriction propagates through the epithelium. These simulations are used to understand the details of the growth process, the effect of the MF on the growth dynamics on the tissue scale, and to make predictions for experimental observations. The avalanches are found to depend on the strength of the apical constriction of cells in the MF, with a stronger apical constriction leading to less frequent and more pronounced avalanches. The results herein highlight the dependence of simulated tissue growth dynamics on relaxation timescales, and serve as a guide for in vitro experiments. Epithelial tissues have interesting properties. They are often described as viscoelastic materials, behaving like an elastic solid on short time scales and as a liquid on long time scales. When tissues proliferate, cell division requires the cells to rearrange and displace each other. To relieve proliferative stress, cells are equipped with machinery that allows them to respond to mechanical cues and rearrange. Herein, we perform computational simulations, based on the vertex model, to investigate epithelial growth. In our simulations, when the tissue size reaches thousands of cells, we observe the prevalence of stochastic step-like growth discontinuities. These newly identified events, which we term avalanches, involve the collective rearrangement of all cells in the tissue, and they are accompanied with localized cellular pressure redistribution and a collective net radial displacement of cells. We study their properties in the simple setting of a spatially uniform and time independent growth model and in the context of an experimentally calibrated Drosophila eye disc growth model. Utilizing the eye disc growth model, we also investigate the relationship between localized cellular mechanical deformations and global growth dynamics. We conclude that avalanches constitute a macroscopic pathway for epithelial tissues to release accumulated proliferative stress when local processes are insufficient.
登录
查看更多内容
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
19.6
作者：
Berthier, Ludovic;Kurchan, Jorge
通讯作者：
Kurchan, Jorge
影响因子：
8.6
作者：
BAK, P;TANG, C;WIESENFELD, K
通讯作者：
WIESENFELD, K
影响因子：
4.6
作者：
Aegerter-Wilmsen, Tinri;Heimlicher, Maria B.;Basler, Konrad
通讯作者：
Basler, Konrad
影响因子：
9.8
作者：
Crossman SH;Streichan SJ;Vincent JP
通讯作者：
Vincent JP