论文标题
三维融合细胞集体的拓扑保护的内部
A topologically-protected interior for three-dimensional confluent cellular collectives
论文作者
论文摘要
器官是体外的细胞集体，其脑状或肠状或类似肾脏的结构出现。为了在其初始发展阶段对细胞集体的形态和流变学做出定量预测，我们构建和研究了三维顶点模型。在这样的模型中，这些细胞被表示为可变形的多面体，具有共享面的细胞，因此它们之间没有间隙，否则称为汇合。在具有周期性边界条件的批量模型中，我们发现刚度过渡是目标单元格索引$ s_0 $的函数，其临界值$ s_0^*= 5.39 \ pm0.01 $。对于具有有限边界的汇合细胞集合，并且在侧面伸长和平面内，径向扩展变形的情况下，我们发现一个显着的边界构造效应是一个单细胞层的厚度。更具体地说，对于横向延伸变形，大体中的细胞与横向变形的方向比对边界的细胞的一致得多。对于平面内的径向变形，散装中的细胞表现出垂直于径向方向的重新定位要比边界处的细胞垂直于径向方向。换句话说，对于这两种变形，大容量，内部细胞都是从变形上拓扑保护的，至少随着时间的流逝，尺度比细胞重排的时间尺度要慢得多，并且最多达到了合理的菌株。我们的结果为类带有一些观察到的细胞形状模式提供了一种基本机制。最后，我们讨论了基于细胞的方法来设计具有新型形态学类型的器官，以研究在多细胞尺度上结构与功能之间的复杂关系。
Organoids are in vitro cellular collectives from which brain-like, or gut-like, or kidney-like structures emerge. To make quantitative predictions regarding the morphology and rheology of a cellular collective in its initial stages of development, we construct and study a three-dimensional vertex model. In such a model, the cells are represented as deformable polyhedrons with cells sharing faces such that there are no gaps between them, otherwise known as confluent. In a bulk model with periodic boundary conditions, we find a rigidity transition as a function of the target cell shape index $s_0$ with a critical value $s_0^*=5.39\pm0.01$. For a confluent cellular collective with a finite boundary, and in the presence of lateral extensile and in-plane, radial extensile deformations, we find a significant boundary-bulk effect that is one-cell layer thick. More specifically, for lateral extensile deformations, the cells in the bulk are much less aligned with the direction of the lateral deformation than the cells at the boundary. For in-plane, radial deformations, the cells in the bulk exhibit much less reorientation perpendicular to the radial direction than the cells at the boundary. In other words, for both deformations, the bulk, interior cells are topologically-protected from the deformations, at least over time scales much slower than the timescale for cellular rearrangements and up to reasonable amounts of strain. Our results provide an underlying mechanism for some observed cell shape patterning in organoids. Finally, we discuss the use of a cellular-based approach to designing organoids with new types of morphologies to study the intricate relationship between structure and function at the multi-cellular scale for example.
