At long time scales, tissue spheroids may flow or appear solid depending on their capacity to reorganize their internal structure. Understanding the relationship between intrinsic mechanical properties at the single cell level, and the tissue spheroids dynamics at the long-time scale is key for artificial tissue constructs, which are assembled from multiple tissue spheroids that over time fuse to form coherent structures. The dynamics of this fusion process are frequently analyzed in the framework of liquid theory, wherein the time scale of coalescence of two droplets is governed by its radius, viscosity and surface tension. In this work, we extend this framework to glassy or jammed cell behavior which can be observed in spheroid fusion. Using simulations of an individual-cell based model, we demonstrate how the spheroid fusion process can be steered from liquid to arrested by varying active cell motility and repulsive energy as established by cortical tension. The divergence of visco-elastic relaxation times indicates glassy relaxation near the transition towards arrested coalescence. Finally, we investigate the role of cell growth in spheroid fusion dynamics. We show that the presence of cell division introduces plasticity in the material and thereby increases coalescence during fusion.

中文翻译：

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活性诱导的流态化在细胞聚集体融合中停滞的凝聚

在长时间范围内，组织球体可能会流动或显示为固体，这取决于它们重组内部结构的能力。了解单细胞水平的内在机械性能与长期尺度上的组织球体动力学之间的关系，对于人工组织构建体至关重要，后者是由多个组织球体组装而成的，随着时间的流逝融合在一起形成相干结构。该融合过程的动力学经常在液体理论的框架内进行分析，其中两个液滴聚结的时间尺度取决于其半径，粘度和表面张力。在这项工作中，我们将此框架扩展到可以在球体融合中观察到的玻璃状或堵塞的细胞行为。使用基于单个细胞的模型的仿真，我们证明了如何通过改变活性细胞的运动性和由皮层张力建立的排斥能来将球状体融合过程从液体引导到停滞。粘弹性弛豫时间的发散表明向着停滞的聚结过渡附近的玻璃状弛豫。最后，我们研究了细胞生长在球体融合动力学中的作用。我们表明细胞分裂的存在在材料中引入可塑性，从而增加融合过程中的聚结。