Abstract
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.
Highlights
Collective epithelial behaviors are essential for the development of lumens in organs
Tube diameter formation involve making use of gels analogous to collagen matrices that encompass cells. Such methods allow epithelial cells to reproduce tissue-like organization[28] and to mimic tubular branching morphogenesis in the presence of growth factors[28,29], the direction of epithelium advancement and lumen formation in gel-based systems is non-controllable, and renders the systematic study of epithelial dynamics in 3D environments very challenging
To further elaborate the dynamics of the tubular epithelial cell sheets (TCSs) coordination, we investigated the variation in the velocity attained by the cell sheets in time and space
Summary
Collective epithelial behaviors are essential for the development of lumens in organs. Tube diameter (μm) formation involve making use of gels analogous to collagen matrices that encompass cells Such methods allow epithelial cells to reproduce tissue-like organization[28] and to mimic tubular branching morphogenesis in the presence of growth factors[28,29], the direction of epithelium advancement and lumen formation in gel-based systems is non-controllable, and renders the systematic study of epithelial dynamics in 3D environments very challenging. To this end, recent studies[25,30] grew cell sheets on the outer surfaces of cylindrical templates with varying diameter to investigate the collective cell behaviors in a more controllable manner. Most of the studies trying to reproduce epithelial cavity networks have aimed at understanding the molecular mechanisms responsible for lumen development, and very few have tried to unravel the dynamical aspects of coordinated epithelial behaviors across space and time
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