Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Soft Matter. 2020 Jul 22;16(28):6572-6581. doi: 10.1039/d0sm00517g.
In both natural and applied contexts, investigating cell self-assembly and aggregation within controlled 3D environments leads to improved understanding of how structured cell assemblies emerge, what determines their shapes and sizes, and whether their structural features are stable. However, the inherent limits of using solid scaffolding or liquid spheroid culture for this purpose restrict experimental freedom in studies of cell self-assembly. Here we investigate multi-cellular self-assembly using a 3D culture medium made from packed microgels as a bridge between the extremes of solid scaffolds and liquid culture. We find that cells dispersed at different volume fractions in this microgel-based 3D culture media aggregate into clusters of different sizes and shapes, forming large system-spanning networks at the highest cell densities. We find that the transitions between different states of assembly can be controlled by the level of cell-cell cohesion and by the yield stress of the packed microgel environment. Measurements of aggregate fractal dimension show that those with increased cell-cell cohesion are less sphere-like and more irregularly shaped, indicating that cell stickiness inhibits rearrangements in aggregates, in analogy to the assembly of colloids with strong cohesive bonds. Thus, the effective surface tension often expected to emerge from increased cell cohesion is suppressed in this type of cell self-assembly.
在自然和应用环境中，研究细胞在受控的 3D 环境中的自组装和聚集，有助于深入了解结构细胞组装体是如何形成的，决定其形状和大小的因素是什么，以及其结构特征是否稳定。然而，由于使用固体支架或液体球体培养方法存在固有局限性，因此在细胞自组装研究中限制了实验自由度。在这里，我们使用由微凝胶组成的 3D 培养基进行多细胞自组装研究，该培养基作为固体支架和液体培养之间的桥梁，从而克服了这些局限性。我们发现，在这种基于微凝胶的 3D 培养基中，以不同体积分数分散的细胞聚集形成不同大小和形状的簇，在最高细胞密度下形成大的系统跨越网络。我们发现，不同组装状态之间的转变可以通过细胞间的内聚力水平和填充微凝胶环境的屈服应力来控制。聚集体分形维数的测量表明，那些具有更高细胞间内聚力的聚集体形状更不规则，不那么球状，这表明细胞粘性抑制了聚集体中的重排，类似于具有强内聚力键的胶体的组装。因此，在这种类型的细胞自组装中，通常预期由于细胞内聚力增加而出现的有效表面张力被抑制。
