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.

集体细胞迁移是整个多细胞生物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板或界面通常是弯曲的，曲率半径与许多细胞长度相当。使用源自人类诱导多能干细胞的人工几何形状和肺泡球，我们在这里展示了细胞感知多细胞尺度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，细胞的聚集性降低，多细胞流场变得更加动态。此外，六角形细胞倾向于聚集成固体状簇，周围是充当背景流体的非六角形细胞。我们建议细胞自然形成六边形组织的簇以最小化自由能，并且这些簇的大小受到弯曲能量损失的限制。我们观察到簇大小随着球体半径的增加而线性增长，这进一步稳定了多细胞流场并增加了细胞的集体性。结果，增加曲率倾向于促进多细胞单层的流动性。总之，这些发现突出了曲率在调节三维多细胞系统的空间和时间特征中的基本作用的潜力。这进一步稳定了多细胞流场并增加了细胞的聚集性。结果，增加曲率倾向于促进多细胞单层的流动性。总之，这些发现突出了曲率在调节三维多细胞系统的空间和时间特征中的基本作用的潜力。这进一步稳定了多细胞流场并增加了细胞的聚集性。结果，增加曲率倾向于促进多细胞单层的流动性。总之，这些发现突出了曲率在调节三维多细胞系统的空间和时间特征中的基本作用的潜力。