In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis.

Autor: Yavitt FM; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA., Kirkpatrick BE; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA.; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Blatchley MR; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA., Speckl KF; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA., Mohagheghian E; Department of Mechanical Science and Engineering, The Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA., Moldovan R; Advanced Light Microscopy Core Facility, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Wang N; Department of Mechanical Science and Engineering, The Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA., Dempsey PJ; Section of Developmental Biology, Department of Pediatrics, University of Colorado, Denver, CO 80204, USA., Anseth KS; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Jan 20; Vol. 9 (3), pp. eadd5668. Date of Electronic Publication: 2023 Jan 20.
DOI: 10.1126/sciadv.add5668
Abstrakt: Spatiotemporally coordinated transformations in epithelial curvature are necessary to generate crypt-villus structures during intestinal development. However, the temporal regulation of mechanotransduction pathways that drive crypt morphogenesis remains understudied. Intestinal organoids have proven useful to study crypt morphogenesis in vitro, yet the reliance on static culture scaffolds limits the ability to assess the temporal effects of changing curvature. Here, a photoinduced hydrogel cross-link exchange reaction is used to spatiotemporally alter epithelial curvature and study how dynamic changes in curvature influence mechanotransduction pathways to instruct crypt morphogenesis. Photopatterned curvature increased membrane tension and depolarization, which was required for subsequent nuclear localization of yes-associated protein 1 (YAP) observed 24 hours following curvature change. Curvature-directed crypt morphogenesis only occurred following a delay in the induction of differentiation that coincided with the delay in spatially restricted YAP localization, indicating that dynamic changes in curvature initiate epithelial curvature-dependent mechanotransduction pathways that temporally regulate crypt morphogenesis.
Databáze: MEDLINE
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