DataSheet1_Activity-Induced Fluidization and Arrested Coalescence in Fusion of Cellular Aggregates.PDF

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 toward 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.

在长时间尺度下，组织球状体（tissue spheroids）可表现为流动态或固态，这取决于其重构内部结构的能力。解析单细胞层面的固有力学特性与长时间尺度下组织球状体动力学之间的关联，是人工组织构建研究的核心议题——人工组织由多个组织球状体组装而成，这些球状体会随时间推移相互融合，最终形成连贯的整体结构。该融合过程的动力学特性通常基于液体理论框架进行分析，其中两个液滴的合并时间尺度由其半径、黏度与表面张力共同决定。本研究将该框架拓展至可在球状体融合过程中观测到的玻璃态或堵塞态细胞行为。通过基于单细胞的模型（individual-cell based model）模拟，我们证实：通过调控由皮层张力（cortical tension）确定的细胞主动运动能力与排斥能，可将球状体融合过程从液态模式调控至停滞模式。黏弹性弛豫时间的发散现象表明，在向停滞合并转变的临界区域附近存在玻璃态弛豫行为。最后，我们探究了细胞生长在球状体融合动力学中的作用，结果显示细胞分裂的存在会赋予材料可塑性，进而提升融合过程中的合并效率。