论文标题
活性驱动的组织比对在增殖的球体中
Activity-driven tissue alignment in proliferating spheroids
论文作者
论文摘要
我们将活性列流体的连续理论扩展到多细胞球体内部的细胞流量和组织动力学,球形,自组装的细胞聚集体被广泛用作研究肿瘤动力学的模型系统。球体表面附近的细胞比资源耗尽的核心中的细胞更好地获取营养,因此更快地增殖。使用分析参数和三维模拟,我们发现增殖梯度会导致流动和活性梯度,这两种梯度都可以使聚集体内部细胞的方向轴对齐。根据环境条件和固有的组织特性,我们确定了三种不同的比对状态:球体,所有细胞在整个聚集体和球体中径向或切向表面与表面和核心径向对齐的角度取向的整个整个骨料和球体对齐。球体内部组织动力学的连续描述不仅使我们能够从实验测量的细胞比对轮廓中推断动态细胞参数,而且更普遍地激发了用于控制聚集物中细胞对齐的新型机制,这些机制已被证明会影响肿瘤的机械性能和侵入性能力。
We extend the continuum theory of active nematic fluids to study cell flows and tissue dynamics inside multicellular spheroids, spherical, self-assembled aggregates of cells that are widely used as model systems to study tumour dynamics. Cells near the surface of spheroids have better access to nutrients and therefore proliferate more rapidly than those in the resource-depleted core. Using both analytical arguments and three-dimensional simulations, we find that the proliferation gradients result in flows and in gradients of activity both of which can align the orientation axis of cells inside the aggregates. Depending on environmental conditions and the intrinsic tissue properties, we identify three distinct alignment regimes: spheroids in which all the cells align either radially or tangentially to the surface throughout the aggregate and spheroids with angular cell orientation close to the surface and radial alignment in the core. The continuum description of tissue dynamics inside spheroids not only allows us to infer dynamic cell parameters from experimentally measured cell alignment profiles, but more generally motivates novel mechanisms for controlling the alignment of cells within aggregates which has been shown to influence the mechanical properties and invasive capabilities of tumors.