Nguyen Kyle C, Jameson Carter D, Baldwin Scott A, Nardini John T, Smith Ralph C, Haugh Jason M, Flores Kevin B
Biomathematics Graduate Program, North Carolina State University, Raleigh, NC 27607, USA; Center for Research in Scientific Computation, North Carolina State University, Raleigh, NC 27607, USA.
Sandia National Laboratories, Albuquerque, NM 87123, USA.
Math Biosci. 2024 Apr;370:109158. doi: 10.1016/j.mbs.2024.109158. Epub 2024 Feb 17.
Fibroblasts in a confluent monolayer are known to adopt elongated morphologies in which cells are oriented parallel to their neighbors. We collected and analyzed new microscopy movies to show that confluent fibroblasts are motile and that neighboring cells often move in anti-parallel directions in a collective motion phenomenon we refer to as "fluidization" of the cell population. We used machine learning to perform cell tracking for each movie and then leveraged topological data analysis (TDA) to show that time-varying point-clouds generated by the tracks contain significant topological information content that is driven by fluidization, i.e., the anti-parallel movement of individual neighboring cells and neighboring groups of cells over long distances. We then utilized the TDA summaries extracted from each movie to perform Bayesian parameter estimation for the D'Orsgona model, an agent-based model (ABM) known to produce a wide array of different patterns, including patterns that are qualitatively similar to fluidization. Although the D'Orsgona ABM is a phenomenological model that only describes inter-cellular attraction and repulsion, the estimated region of D'Orsogna model parameter space was consistent across all movies, suggesting that a specific level of inter-cellular repulsion force at close range may be a mechanism that helps drive fluidization patterns in confluent mesenchymal cell populations.
已知在汇合的单层中的成纤维细胞会呈现出细长的形态,其中细胞与相邻细胞平行排列。我们收集并分析了新的显微镜视频,以表明汇合的成纤维细胞是可移动的,并且相邻细胞在一种我们称为细胞群体“流化”的集体运动现象中经常沿反平行方向移动。我们使用机器学习对每个视频进行细胞跟踪,然后利用拓扑数据分析(TDA)表明,由跟踪产生的随时间变化的点云包含由流化驱动的重要拓扑信息内容,即单个相邻细胞和相邻细胞群在长距离上的反平行运动。然后,我们利用从每个视频中提取的TDA总结对D'Orsgona模型进行贝叶斯参数估计,D'Orsgona模型是一种基于代理的模型(ABM),已知会产生各种各样不同的模式,包括在质量上与流化相似的模式。尽管D'Orsgona ABM是一个仅描述细胞间吸引和排斥的现象学模型,但D'Orsogna模型参数空间的估计区域在所有视频中都是一致的,这表明近距离处特定水平的细胞间排斥力可能是有助于驱动汇合间充质细胞群体中流化模式的一种机制。
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