Mechanoresponse of Curved Epithelial Monolayers Lining Bowl-Shaped 3D Microwells.

The optimal functioning of many organs relies on the curved architecture of their epithelial tissues. However, the mechanoresponse of epithelia to changes in curvature remains misunderstood. Here, we designed bowl-shaped microwells in hydrogels via photopolymerization to faithfully replicate the shape and dimensions of lobular structures. Leveraging these hydrogel-based microwells, we engineered curved epithelial monolayers and investigated how in-plane and Gaussian curvatures at the microwell entrance influence epithelial behavior. Cells and nuclei around the microwell edge displayed a more pronounced centripetal orientation as the in-plane curvature decreases, and enhanced cell straightness and speed. Moreover, cells reorganized their actin cytoskeleton by forming a supracellular actin cable at the microwell edge, with its size becoming more pronounced as the in-plane curvature decreased. The Gaussian curvature at the microwell entrance enhanced the maturation of the supracellular actin cable architecture and led to a vertical orientation of nuclei towards the bottom of the microwell. Increasing Gaussian curvature resulted in flattened and elongated nuclear morphologies characterized by highly compacted chromatin states.  Our approach provides a better understanding of the mechanoresponse of curved epithelial monolayers curvatures lining lobular structures. Additionally, bowl-shaped microwells offer a powerful platform to study curvature-dependent mechanotransduction pathways in anatomically relevant 3D structures. This article is protected by copyright. All rights reserved.