G. Millán Institute for Fluid Dynamics, Nanoscience & Industrial Mathematics, and Department of Mathematics, Universidad Carlos III de Madrid, Leganés, Spain.
Courant Institute of Mathematical Sciences, New York University, New York, United States of America.
PLoS Comput Biol. 2020 Dec 23;16(12):e1008407. doi: 10.1371/journal.pcbi.1008407. eCollection 2020 Dec.
By modifying and calibrating an active vertex model to experiments, we have simulated numerically a confluent cellular monolayer spreading on an empty space and the collision of two monolayers of different cells in an antagonistic migration assay. Cells are subject to inertial forces and to active forces that try to align their velocities with those of neighboring ones. In agreement with experiments in the literature, the spreading test exhibits formation of fingers in the moving interfaces, there appear swirls in the velocity field, and the polar order parameter and the correlation and swirl lengths increase with time. Numerical simulations show that cells inside the tissue have smaller area than those at the interface, which has been observed in recent experiments. In the antagonistic migration assay, a population of fluidlike Ras cells invades a population of wild type solidlike cells having shape parameters above and below the geometric critical value, respectively. Cell mixing or segregation depends on the junction tensions between different cells. We reproduce the experimentally observed antagonistic migration assays by assuming that a fraction of cells favor mixing, the others segregation, and that these cells are randomly distributed in space. To characterize and compare the structure of interfaces between cell types or of interfaces of spreading cellular monolayers in an automatic manner, we apply topological data analysis to experimental data and to results of our numerical simulations. We use time series of data generated by numerical simulations to automatically group, track and classify the advancing interfaces of cellular aggregates by means of bottleneck or Wasserstein distances of persistent homologies. These techniques of topological data analysis are scalable and could be used in studies involving large amounts of data. Besides applications to wound healing and metastatic cancer, these studies are relevant for tissue engineering, biological effects of materials, tissue and organ regeneration.
通过修改和校准主动顶点模型以适应实验,我们对以下两种情况进行了数值模拟:一个空的空间上的融合细胞单层的扩展,以及在拮抗迁移实验中两个不同细胞单层的碰撞。细胞受到惯性力和主动力的作用,这些力试图使它们的速度与相邻细胞的速度保持一致。与文献中的实验结果一致,扩展测试在移动界面上显示出手指的形成,速度场中出现漩涡,极性序参量、相关长度和漩涡长度随时间增加。数值模拟表明,组织内部的细胞面积小于界面处的细胞面积,这在最近的实验中已经观察到。在拮抗迁移实验中,一群流体状 Ras 细胞入侵了一群具有分别高于和低于几何临界值的形状参数的野生型固态细胞。细胞混合或分离取决于不同细胞之间的连接张力。通过假设一部分细胞有利于混合,另一部分细胞有利于分离,并且这些细胞在空间中随机分布,我们再现了实验中观察到的拮抗迁移实验。为了自动地对细胞类型之间的界面或扩展细胞单层的界面的结构进行特征描述和比较,我们将拓扑数据分析应用于实验数据和我们的数值模拟结果。我们使用数值模拟生成的时间序列数据,通过瓶颈或 Wasserstein 距离的持久同调,自动对细胞聚集体的推进界面进行分组、跟踪和分类。这些拓扑数据分析技术具有可扩展性,可以用于涉及大量数据的研究。除了在伤口愈合和转移性癌症中的应用外,这些研究还与组织工程、材料的生物学效应、组织和器官再生相关。
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