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

Author:

Yavitt F. Max12ORCID,Kirkpatrick Bruce E.123,Blatchley Michael R.12ORCID,Speckl Kelly F.12ORCID,Mohagheghian Erfan4ORCID,Moldovan Radu5,Wang Ning4ORCID,Dempsey Peter J.6,Anseth Kristi S.12ORCID

Affiliation:

1. Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, USA.

2. BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309, USA.

3. Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

4. Department of Mechanical Science and Engineering, The Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

5. Advanced Light Microscopy Core Facility, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

6. Section of Developmental Biology, Department of Pediatrics, University of Colorado, Denver, CO 80204, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3