Physical Mechanisms Driving Cell Sorting in &ITHydra&IT
Physical Mechanisms Driving Cell Sorting in &ITHydra&IT
复制标题
DOI：
10.1016/j.bpj.2017.10.045
复制
发表时间：
2017-12-19
影响因子：
3.4
通讯作者：
Collins, Eva-Maria S.
中科院分区：
文献类型：
--
作者：
Cochet-Escartin, Olivier;Locke, Tiffany T.;Collins, Eva-Maria S.
细胞分选，即异质细胞混合物组织成不同的组织，是发育中的基本模式化过程。Hydra是进行三维细胞分选研究的强大模型系统，因为它具有在完全解离成单个细胞后再生的独特能力。物理学家Alfred Gierer和Hans Meinhardt在40多年前就认识到了Hydra的自组织特性。然而，在水螅从细胞聚集体再生过程中，是什么驱动细胞分选仍然存在争议。差异运动和差异粘附已被提出作为驱动机制，但现有的实验数据不足以区分这两个。在这里，我们回答这个长期存在的问题，通过使用转基因水螅表达荧光蛋白和多尺度的实验和数值方法。通过量化单细胞和整个聚集体行为的运动学，我们表明，细胞类型之间存在细胞运动性没有差异，分选动力学遵循幂律，指数类似于0.5。此外，我们测量分离组织的物理特性，并量化其粘度和表面张力。基于我们的实验结果和数值模拟，我们得出结论，组织界面张力足以解释水螅细胞聚集体中的细胞分选。此外，我们证明了在排序过程中聚集体的几何形状是理解排序动力学的关键，并解释了幂律行为的指数。我们的研究结果回答了长期存在的问题，驱动水螅细胞聚集体中细胞分选的物理机制。此外，他们还展示了这种生物体对于自组织和模式形成的生物物理研究是多么强大。
Cell sorting, whereby a heterogeneous cell mixture organizes into distinct tissues, is a fundamental patterning process in development. Hydra is a powerful model system for carrying out studies of cell sorting in three dimensions, because of its unique ability to regenerate after complete dissociation into individual cells. The physicists Alfred Gierer and Hans Meinhardt recognized Hydra's self-organizing properties more than 40 years ago. However, what drives cell sorting during regeneration of Hydra from cell aggregates is still debated. Differential motility and differential adhesion have been proposed as driving mechanisms, but the available experimental data are insufficient to distinguish between these two. Here, we answer this longstanding question by using transgenic Hydra expressing fluorescent proteins and a multiscale experimental and numerical approach. By quantifying the kinematics of single cell and whole aggregate behaviors, we show that no differences in cell motility exist among cell types and that sorting dynamics follow a power law with an exponent of similar to 0.5. Additionally, we measure the physical properties of separated tissues and quantify their viscosities and surface tensions. Based on our experimental results and numerical simulations, we conclude that tissue interfacial tensions are sufficient to explain cell sorting in aggregates of Hydra cells. Furthermore, we demonstrate that the aggregate's geometry during sorting is key to understanding the sorting dynamics and explains the exponent of the power law behavior. Our results answer the long standing question of the physical mechanisms driving cell sorting in Hydra cell aggregates. In addition, they demonstrate how powerful this organism is for biophysical studies of self-organization and pattern formation.