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Title: Geometry-mediated bridging drives nonadhesive stripe wound healing
Authors: Xu, Hongmei
Huo, Yucheng
Zhou, Quan
Wang, Abraham Lianghao
Cai, Pingqiang
Doss, Bryant
Huang, Changjin
Hsia, K. Jimmy
Keywords: Engineering::Bioengineering
Issue Date: 2023
Source: 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-.
Project: M4082428.050 
Journal: Proceedings of the National Academy of Sciences 
Abstract: 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.
ISSN: 0027-8424
DOI: 10.1073/pnas.2221040120
Schools: School of Mechanical and Aerospace Engineering 
School of Chemistry, Chemical Engineering and Biotechnology 
Rights: © 2023 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:MAE Journal Articles

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