Geometry-mediated bridging drives nonadhesive stripe wound healing

Wound healing through reepithelialization of gaps is of profound importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse-string constriction. However, the...

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Main Authors: Xu, Hongmei, Huo, Yucheng, Zhou, Quan, Wang, Abraham Lianghao, Cai, Pingqiang, Doss, Bryant, Huang, Changjin, Hsia, K. Jimmy
Other Authors: School of Mechanical and Aerospace Engineering
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/170112
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1701122023-09-02T16:48:13Z Geometry-mediated bridging drives nonadhesive stripe wound healing Xu, Hongmei Huo, Yucheng Zhou, Quan Wang, Abraham Lianghao Cai, Pingqiang Doss, Bryant Huang, Changjin Hsia, K. Jimmy School of Mechanical and Aerospace Engineering School of Chemistry, Chemical Engineering and Biotechnology Engineering::Bioengineering Gap Closure Collective Cell Migration Wound healing through reepithelialization of gaps is of profound importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse-string constriction. However, the studies to date have not separated the gap-edge curvature effect from the gap size effect. Here, we fabricate micropatterned hydrogel substrates with long, straight, and wavy non-cell-adhesive stripes of different gap widths to investigate the stripe edge curvature and stripe width effects on the reepithelialization of Madin-Darby canine kidney (MDCK) cells. Our results show that MDCK cell reepithelization is closely regulated by the gap geometry and may occur through different pathways. In addition to purse-string contraction, we identify gap bridging either via cell protrusion or by lamellipodium extension as critical cellular and molecular mechanisms for wavy gap closure. Cell migration in the direction perpendicular to wound front, sufficiently small gap size to allow bridging, and sufficiently high negative curvature at cell bridges for actin cable constriction are necessary/sufficient conditions for gap closure. Our experiments demonstrate that straight stripes rarely induce cell migration perpendicular to wound front, but wavy stripes do; cell protrusion and lamellipodia extension can help establish bridges over gaps of about five times the cell size, but not significantly beyond. Such discoveries deepen our understanding of mechanobiology of cell responses to curvature and help guide development of biophysical strategies for tissue repair, plastic surgery, and better wound management. Ministry of Education (MOE) Nanyang Technological University Published version K.J.H. and H.X. would like to acknowledge the financial support from Nanyang Technological University (Grant M4082428.050). C.H. acknowledges financial support from Nanyang Technological University (Startup Grant M4082352) and Ministry of Education (MOE), Singapore, under its Academic Research Fund Tier 2 (MOE-T2EP50121-0004). H.X. would like to acknowledge the Research Scholarship awarded by Nanyang Technological University. 2023-08-28T08:06:12Z 2023-08-28T08:06:12Z 2023 Journal Article Xu, H., Huo, Y., Zhou, Q., Wang, A. L., Cai, P., Doss, B., Huang, C. & Hsia, K. J. (2023). Geometry-mediated bridging drives nonadhesive stripe wound healing. Proceedings of the National Academy of Sciences, 120(18), e2221040120-. https://dx.doi.org/10.1073/pnas.2221040120 0027-8424 https://hdl.handle.net/10356/170112 10.1073/pnas.2221040120 37098071 2-s2.0-85153901039 18 120 e2221040120 en M4082428.050 M4082352 MOE-T2EP50121-0004 Proceedings of the National Academy of Sciences © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Engineering::Bioengineering
Gap Closure
Collective Cell Migration
spellingShingle Engineering::Bioengineering
Gap Closure
Collective Cell Migration
Xu, Hongmei
Huo, Yucheng
Zhou, Quan
Wang, Abraham Lianghao
Cai, Pingqiang
Doss, Bryant
Huang, Changjin
Hsia, K. Jimmy
Geometry-mediated bridging drives nonadhesive stripe wound healing
description Wound healing through reepithelialization of gaps is of profound importance to the medical community. One critical mechanism identified by researchers for closing non-cell-adhesive gaps is the accumulation of actin cables around concave edges and the resulting purse-string constriction. However, the studies to date have not separated the gap-edge curvature effect from the gap size effect. Here, we fabricate micropatterned hydrogel substrates with long, straight, and wavy non-cell-adhesive stripes of different gap widths to investigate the stripe edge curvature and stripe width effects on the reepithelialization of Madin-Darby canine kidney (MDCK) cells. Our results show that MDCK cell reepithelization is closely regulated by the gap geometry and may occur through different pathways. In addition to purse-string contraction, we identify gap bridging either via cell protrusion or by lamellipodium extension as critical cellular and molecular mechanisms for wavy gap closure. Cell migration in the direction perpendicular to wound front, sufficiently small gap size to allow bridging, and sufficiently high negative curvature at cell bridges for actin cable constriction are necessary/sufficient conditions for gap closure. Our experiments demonstrate that straight stripes rarely induce cell migration perpendicular to wound front, but wavy stripes do; cell protrusion and lamellipodia extension can help establish bridges over gaps of about five times the cell size, but not significantly beyond. Such discoveries deepen our understanding of mechanobiology of cell responses to curvature and help guide development of biophysical strategies for tissue repair, plastic surgery, and better wound management.
author2 School of Mechanical and Aerospace Engineering
author_facet School of Mechanical and Aerospace Engineering
Xu, Hongmei
Huo, Yucheng
Zhou, Quan
Wang, Abraham Lianghao
Cai, Pingqiang
Doss, Bryant
Huang, Changjin
Hsia, K. Jimmy
format Article
author Xu, Hongmei
Huo, Yucheng
Zhou, Quan
Wang, Abraham Lianghao
Cai, Pingqiang
Doss, Bryant
Huang, Changjin
Hsia, K. Jimmy
author_sort Xu, Hongmei
title Geometry-mediated bridging drives nonadhesive stripe wound healing
title_short Geometry-mediated bridging drives nonadhesive stripe wound healing
title_full Geometry-mediated bridging drives nonadhesive stripe wound healing
title_fullStr Geometry-mediated bridging drives nonadhesive stripe wound healing
title_full_unstemmed Geometry-mediated bridging drives nonadhesive stripe wound healing
title_sort geometry-mediated bridging drives nonadhesive stripe wound healing
publishDate 2023
url https://hdl.handle.net/10356/170112
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