学习单个和集体细胞迁移的动态模型:综述

David B. Brückner, Chase P. Broedersz
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摘要

单个和集体细胞迁移是胚胎发育、免疫反应、伤口愈合和癌症转移等生理现象的重要基础过程。为了从物理角度理解细胞迁移,已经开发了各种各样的控制细胞运动的潜在物理机制的模型。发展此类模型的一个关键挑战是如何将它们与实验观察联系起来,而实验观察往往表现出复杂的随机行为。在这篇综述中,我们讨论了数据驱动理论方法的最新进展,这些方法直接与实验数据联系起来,推断随机细胞迁移的动态模型。利用纳米制造、图像分析和跟踪技术的进步,实验研究现在提供了前所未有的细胞动力学大数据集。与此同时,理论上的努力已经指向将这些数据集整合到从单细胞到组织尺度的物理模型中,目的是概念化细胞的涌现行为。我们首先回顾了这个推理问题是如何在二维基底和结构化限制系统中自由迁移的细胞中解决的。此外,我们讨论了数据驱动的方法如何与分子机制联系起来,无论是通过整合机械自下而上的生物物理模型,还是通过对亚细胞自由度进行推理。最后,我们概述了数据驱动建模在开发细胞间行为可变性框架以及学习多细胞系统集体动力学方面的应用。具体来说,我们回顾了恢复细胞相互作用和集体动力模式的推理和机器学习方法,以及如何将这些方法集成到集体迁移的物理活性物质模型中。
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Learning dynamical models of single and collective cell migration: a review
Single and collective cell migration are fundamental processes critical for physiological phenomena ranging from embryonic development and immune response to wound healing and cancer metastasis. To understand cell migration from a physical perspective, a broad variety of models for the underlying physical mechanisms that govern cell motility have been developed. A key challenge in the development of such models is how to connect them to experimental observations, which often exhibit complex stochastic behaviours. In this review, we discuss recent advances in data-driven theoretical approaches that directly connect with experimental data to infer dynamical models of stochastic cell migration. Leveraging advances in nanofabrication, image analysis, and tracking technology, experimental studies now provide unprecedented large datasets on cellular dynamics. In parallel, theoretical efforts have been directed towards integrating such datasets into physical models from the single cell to the tissue scale with the aim of conceptualizing the emergent behavior of cells. We first review how this inference problem has been addressed in freely migrating cells on two-dimensional substrates and in structured, confining systems. Moreover, we discuss how data-driven methods can be connected with molecular mechanisms, either by integrating mechanistic bottom-up biophysical models, or by performing inference on subcellular degrees of freedom. Finally, we provide an overview of applications of data-driven modelling in developing frameworks for cell-to-cell variability in behaviours, and for learning the collective dynamics of multicellular systems. Specifically, we review inference and machine learning approaches to recover cell-cell interactions and collective dynamical modes, and how these can be integrated into physical active matter models of collective migration.
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