Lange Zoë, Matthäus Franziska, Qiu Mingfeng
Frankfurt Institute for Advanced Studies, Frankfurt am Main, Germany.
Department of Physics, Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
PLoS Comput Biol. 2025 May 21;21(5):e1012993. doi: 10.1371/journal.pcbi.1012993. eCollection 2025 May.
Vertex models provide a robust theoretical framework for studying epithelial tissues as a network of cell boundaries. They have been pivotal in exploring properties such as cell packing geometry and rigidity transitions. Recently, extended vertex models have become instrumental in bridging the subcellular scales to the tissue scale. Here, we review extensions of the model aiming to capture experimentally observed subcellular features of epithelial tissues including heterogeneity in myosin activity across the tissue, non-uniform contractility structures, and mechanosensitive feedback loops. We discuss how these extensions change and challenge current perspectives on observables of macroscopic tissue properties. First, we find that extensions to the vertex model can change model properties significantly, impacting the critical threshold and in some cases even the existence of a rigidity transition. Second, we find that packing disorder can be explained by models employing different subcellular mechanisms, indicating a source of stochasticity and gradual local size changes as common mesoscopic motifs in the mechanics of tissue organization. We address complementary models and statistical inference, putting vertex models in a broader methodological context and we give a brief overview of software packages utilized in increasingly complex vertex model studies. Our review emphasizes the need for more comparative, systematic studies that identify specific classes of vertex models which share a set of well-defined properties, as well as a more in-depth discussion of modeling choices and their biological motivations.
顶点模型为将上皮组织作为细胞边界网络进行研究提供了一个强大的理论框架。它们在探索诸如细胞堆积几何形状和刚性转变等特性方面发挥了关键作用。最近,扩展顶点模型在连接亚细胞尺度和组织尺度方面发挥了重要作用。在这里,我们回顾了该模型的扩展,旨在捕捉上皮组织实验观察到的亚细胞特征,包括整个组织中肌球蛋白活性的异质性、非均匀收缩结构和机械敏感反馈回路。我们讨论了这些扩展如何改变并挑战当前对宏观组织特性可观测值的看法。首先,我们发现顶点模型的扩展可以显著改变模型特性,影响临界阈值,在某些情况下甚至影响刚性转变的存在。其次,我们发现堆积无序可以由采用不同亚细胞机制的模型来解释,这表明随机性来源和逐渐的局部大小变化是组织力学中常见的介观模式。我们讨论了互补模型和统计推断,将顶点模型置于更广泛的方法背景中,并简要概述了在日益复杂的顶点模型研究中使用的软件包。我们的综述强调需要进行更多比较性、系统性的研究,以确定具有一组明确属性的特定类别的顶点模型,以及对建模选择及其生物学动机进行更深入的讨论。