Collective curvature sensing and fluidity in three-dimensional multicellular systems
Collective curvature sensing and fluidity in three-dimensional multicellular systems
复制标题
DOI：
10.1038/s41567-022-01747-0
复制
发表时间：
2022-10
期刊：
影响因子：
19.6
通讯作者：
Wen-Lang Tang;Amit Das;A. Pegoraro;Y. Han;Jessie Huang;David A. Roberts;Haiqian Yang;J. Fredberg;D. Kotton;Dapeng Bi;Ming Guo
中科院分区：
文献类型：
--
作者：
Wen-Lang Tang;Amit Das;A. Pegoraro;Y. Han;Jessie Huang;David A. Roberts;Haiqian Yang;J. Fredberg;D. Kotton;Dapeng Bi;Ming Guo
集体细胞迁移是多细胞生物体生命中的一个重要过程，例如在胚胎发育、伤口愈合和肿瘤转移中。与这些过程相关的基底或界面通常是弯曲的，其曲率半径与许多电池长度相当。使用人工几何形状和来自人类诱导多能干细胞的肺泡球，在这里，我们表明细胞感知多细胞尺度的曲率，并且它在调节集体细胞迁移中起作用。随着单层曲率的增加，细胞减少其集体性和多细胞流场变得更加动态。此外，六边形形状的细胞倾向于聚集成固体状的簇，这些簇被充当背景流体的非六边形细胞包围。我们建议，细胞自然形成六边形组织的集群，以尽量减少自由能，这些集群的大小是有限的弯曲能量惩罚。我们观察到，集群的大小线性增长的球体半径的增加，这进一步稳定了多细胞流场，并增加细胞的集体。因此，增加曲率倾向于促进多细胞单层中的流动性。总之，这些发现突出了潜在的基本作用，曲率在调节三维多细胞系统的空间和时间特性。
Collective cell migration is an essential process throughout the lives of multicellular organisms, for example in embryonic development, wound healing and tumour metastasis. Substrates or interfaces associated with these processes are typically curved, with radii of curvature comparable to many cell lengths. Using both artificial geometries and lung alveolospheres derived from human induced pluripotent stem cells, here we show that cells sense multicellular-scale curvature and that it plays a role in regulating collective cell migration. As the curvature of a monolayer increases, cells reduce their collectivity and the multicellular flow field becomes more dynamic. Furthermore, hexagonally shaped cells tend to aggregate in solid-like clusters surrounded by non-hexagonal cells that act as a background fluid. We propose that cells naturally form hexagonally organized clusters to minimize free energy, and the size of these clusters is limited by a bending energy penalty. We observe that cluster size grows linearly as sphere radius increases, which further stabilizes the multicellular flow field and increases cell collectivity. As a result, increasing curvature tends to promote the fluidity in multicellular monolayer. Together, these findings highlight the potential for a fundamental role of curvature in regulating both spatial and temporal characteristics of three-dimensional multicellular systems.