Continuum theory for confluent cell monolayers: Interplay between cell growth, division, and intercalation
Continuum theory for confluent cell monolayers: Interplay between cell growth, division, and intercalation
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DOI：
10.1016/j.jmps.2023.105443
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发表时间：
2023-09
影响因子：
5.3
通讯作者：
Prakhar Bandil;Franck J. Vernerey
中科院分区：
文献类型：
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作者：
Prakhar Bandil;Franck J. Vernerey
动态细胞活动产生的机械力在生物组织的形态发生和生长中起着至关重要的作用。虽然力学的影响是显而易见的，但关于机械力如何在汇合细胞群水平上与生物过程进行交流的方式出现了许多问题。在数学模型的开发中可能会找到一些答案，这些模型能够根据个体规则（单细胞反应）描述大量活性剂的新兴行为。从这个角度来看，目前的工作提出了一个连续尺度模型，可以在平均意义上捕获有或没有外部机械约束的汇合组织的主动力学和演化。为此，我们将汇合细胞群（单层）概念化为可变形的动态网络，其中单个细胞可以通过交换邻居或分裂来修改其邻域的拓扑结构。通过这种描述，我们使用统计力学和瞬态网络理论的概念来推导等效的主动粘弹性连续体模型，该模型可以在宏观尺度上概括底层网络的一些显着特征。不失一般性，这里假设细胞网络遵循顶点模型模拟中使用的众所周知的规则，这些规则是：（a）基于其体积和皮质弹性的细胞弹性，（b）细胞嵌入（或T1转变），以及（c）细胞增殖（扩张和分裂）。我们通过示例和插图表明，该模型能够表征机械力和生物过程之间的复杂串扰，这可能会驱动细胞聚集体的紧急生长和变形。
Mechanical forces generated by dynamic cellular activities play a crucial role in the morphogenesis and growth of biological tissues. While the influence of mechanics is clear, many questions arise regarding the way by which mechanical forces communicate with biological processes at the level of a confluent cell population. Some answers may be found in the development of mathematical models that are capable of describing the emerging behavior of a large population of active agents based on individualistic rules (single-cell response). In this perspective, the present work presents a continuum-scale model that can capture, in an average sense, the active mechanics and evolution of a confluent tissue with or without external mechanical constraints. For this, we conceptualize a confluent cell population (in a monolayer) as a deformable dynamic network, where a single cell can modify the topology of its neighborhood by swapping neighbors or dividing. With this description, we use concepts from statistical mechanics and the transient network theory to derive an equivalent active visco-elastic continuum model, which can recapitulate some of the salient features of the underlying network at the macroscale. Without loss of generality, the cell network is here assumed to follow well-known rules used in vertex model simulations, which are: (a) cell elasticity based on its bulk and cortical elasticity, (b) cell intercalation (or T1 transition), and (c) cell proliferation (expansion and division). We show, through examples and illustrations, that the model is able to characterize complex cross-talk between mechanical forces and biological processes, which are likely to drive the emergent growth and deformation of cell aggregates.