CompuCell3D Simulations Reproduce Mesenchymal Cell Migration on Flat Substrates.

CompuCell3D Simulations Reproduce Mesenchymal Cell Migration on Flat Substrates.
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CompuCell3D 模拟再现平坦基底上的间充质细胞迁移。

DOI:
10.1016/j.bpj.2020.04.024
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发表时间:
2020
影响因子:
3.4
通讯作者:
deAlmeida,RitaMC
deAlmeida,RitaMC
中科院分区:
生物学3区
文献类型:
--
作者:
Fortuna,Ismael;Perrone,GabrielC;Krug,MoniqueS;Susin,Eduarda;Belmonte,JulioM;Thomas,GilbertoL;Glazier,JamesA;deAlmeida,RitaMC

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间充质细胞的爬行在正常发育、组织功能和许多疾病中都是一个关键过程。因此,细胞爬行的定量预测数值模拟具有多种科学、医学和技术应用。然而,我们仍然缺乏一种低计算成本的方法来模拟间充质三维(3D)细胞爬行。在这里,我们开发了一个易于计算的3D模型(在CompuCell3D模拟环境中实现),即在二维基质上爬行的间充质细胞。Fürth方程是迁移细胞均方位移(MSD)曲线的通常表征,它描述了随着时间间隔的增加,细胞运动从弹道区域过渡到扩散区域的运动。最近的实验表明,在很短的时间间隔内,细胞表现出额外的快速扩散机制。我们的模拟的MSD曲线再现了实验观察到的三种时间区域,即短时间间隔的快速扩散、长时间间隔的缓慢扩散和中间时间间隔-弹道运动。由此产生的实验和模拟轨迹的参数化允许定义在计算单位和实验室单位之间转换的时间和长度尺度。通过这些标度的重新标度,可以在MSD曲线之间以及来自实验和模拟的速度自相关函数之间进行直接的定量比较。虽然我们的模拟复制了实验中观察到的自发对称性破缺、短时间尺度扩散运动和自发细胞运动重定向,但它们的计算成本很低,允许它们用于多尺度虚拟组织模拟。实验和模拟细胞运动的比较支持这样的假设,即短期肌球蛋白动力学影响较长时间的细胞运动。基本细胞迁移模拟模型的成功预示着它在更复杂的情况下的应用,包括趋化作用、通过复杂的3D基质的迁移以及细胞的集体运动。
Mesenchymal cell crawling is a critical process in normal development, in tissue function, and in many diseases. Quantitatively predictive numerical simulations of cell crawling thus have multiple scientific, medical, and technological applications. However, we still lack a low-computational-cost approach to simulate mesenchymal three-dimensional (3D) cell crawling. Here, we develop a computationally tractable 3D model (implemented as a simulation in the CompuCell3D simulation environment) of mesenchymal cells crawling on a two-dimensional substrate. The Fürth equation, the usual characterization of mean-squared displacement (MSD) curves for migrating cells, describes a motion in which, for increasing time intervals, cell movement transitions from a ballistic to a diffusive regime. Recent experiments have shown that for very short time intervals, cells exhibit an additional fast diffusive regime. Our simulations'MSDcurves reproduce the three experimentally observed temporal regimes, with fast diffusion for short time intervals, slow diffusion for long time intervals, and intermediate time -interval-ballistic motion. The resulting parameterization of the trajectories for both experiments and simulations allows the definition of time- and length scales that translate between computational and laboratory units. Rescaling by these scales allows direct quantitative comparisons amongMSDcurves and between velocity autocorrelation functions from experiments and simulations. Although our simulations replicate experimentally observed spontaneous symmetry breaking, short-timescale diffusive motion, and spontaneous cell-motion reorientation, their computational cost is low, allowing their use in multiscale virtual-tissue simulations. Comparisons between experimental and simulated cell motion support the hypothesis that short-time actomyosin dynamics affects longer-time cell motility. The success of the base cell-migration simulation model suggests its future application in more complex situations, including chemotaxis, migration through complex 3D matrices, and collective cell motion.
DOI: 10.1101/cshperspect.a002980
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DOI: --
发表时间: 2011
影响因子: 3.8
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DOI: --
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