An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration.

An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration.
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DOI:
10.3389/fcell.2020.615759
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发表时间:
2020
影响因子:
5.5
通讯作者:
Grecco HE
Grecco HE
中科院分区:
生物学2区
文献类型:
--
作者:
Cuenca MB;Canedo L;Perez-Castro C;Grecco HE

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细胞迁移已经成为各种生物系统中的研究主题,从发育期间的形态发生事件到癌症进展。在这项工作中,我们在一个模块化的框架中描述了单细胞运动,从中我们模拟了胶质母细胞瘤细胞的集体行为,胶质母细胞瘤是最普遍和恶性的原发性脑肿瘤。我们使用了U87细胞系,它可以作为单层生长,也可以在空间上紧密堆积并组织在称为球体的3D结构中。我们的综合模型认为,最相关的机制参与细胞迁移:趋化性的吸引因子,机械相互作用和随机运动。每种机制的影响都被集成到细胞向特定方向移动的总体概率中,以类似自动机的方式。我们的模拟拟合并再现了一组迁移试验中球体的涌现行为,其中跟踪了单细胞轨迹。我们还预测了迁移抑制的影响,从简单的实验表征的单一处理的细胞轨道的集落。允许补充迁移细胞行为中的分子知识的工具的开发与理解基本细胞过程相关,包括生理学(例如器官形成,组织再生等)和病理学观点。总的来说,这是一个多功能的工具,已被证明可以预测U87细胞中的个体和集体行为,但可以应用于各种各样的场景。
Cell migration has been a subject of study in a broad variety of biological systems, from morphogenetic events during development to cancer progression. In this work, we describe single-cell movement in a modular framework from which we simulate the collective behavior of glioblastoma cells, the most prevalent and malignant primary brain tumor. We used the U87 cell line, which can be grown as a monolayer or spatially closely packed and organized in 3D structures called spheroids. Our integrative model considers the most relevant mechanisms involved in cell migration: chemotaxis of attractant factor, mechanical interactions and random movement. The effect of each mechanism is integrated into the overall probability of the cells to move in a particular direction, in an automaton-like approach. Our simulations fit and reproduced the emergent behavior of the spheroids in a set of migration assays where single-cell trajectories were tracked. We also predicted the effect of migration inhibition on the colonies from simple experimental characterization of single treated cell tracks. The development of tools that allow complementing molecular knowledge in migratory cell behavior is relevant for understanding essential cellular processes, both physiological (such as organ formation, tissue regeneration among others) and pathological perspectives. Overall, this is a versatile tool that has been proven to predict individual and collective behavior in U87 cells, but that can be applied to a broad variety of scenarios.
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