Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore, 117411, Singapore.
Centre for Advanced 2D Materials and Graphene Research Centre, National University of Singapore, 6 Science Drive 2, Singapore, 117546, Singapore.
Nat Commun. 2017 Nov 15;8(1):1517. doi: 10.1038/s41467-017-01390-x.
Collective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1-10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical-basal polarity, and have actin alignment, cell orientation, tissue organization, and migration modes that depend on the extent of tubular confinement and/or curvature. In contrast to flat constraint, the cell sheets in a highly constricted smaller microtube demonstrate slow motion with periodic relaxation, but fast overall movement in large microtubes. Altogether, our findings provide insights into the emerging migratory modes for epithelial migration and growth under tubular confinement, which are reminiscent of the in vivo scenario.
上皮细胞的集体行为对于器官中空腔的形成至关重要。然而，传统的平面系统检测方法无法复制管状结构的细胞群体，这些细胞群体以协同的方式在平面外的弯曲和受限表面上推进，例如体内的导管伸长。在这里，我们通过在直径为 1-10 个细胞长度的微管内形成上皮细胞片的管腔来模拟这种协调的组织迁移。我们表明，这些细胞管重现了生理的顶底极性，并且具有肌动蛋白排列、细胞取向、组织组织和迁移模式，这些模式取决于管状限制和/或曲率的程度。与平面约束相反，在高度受限的较小微管中的细胞片显示出周期性松弛的缓慢运动，但在较大微管中则表现出快速的整体运动。总的来说，我们的发现为上皮细胞在管状约束下迁移和生长的新兴迁移模式提供了深入的了解，这让人联想到体内的情况。
