Gap geometry dictates epithelial closure efficiency

• Published in: Nature communications 2015-07, Vol.6 (1), p.7683-7683, Article 7683
• Main Authors: Ravasio, Andrea, Cheddadi, Ibrahim, Chen, Tianchi, Pereira, Telmo, Ong, Hui Ting, Bertocchi, Cristina, Brugues, Agusti, Jacinto, Antonio, Kabla, Alexandre J., Toyama, Yusuke, Trepat, Xavier, Gov, Nir, Neves de Almeida, Luís, Ladoux, Benoit
• Format: Article
• Language: English
• Subjects: 13/106; 14/35; 14/63; 631/80/79/1987; 631/80/84; 9/10; Actomyosin - metabolism; Analysis of PDEs; Animals; Biochemistry, Molecular Biology; Biomechanics; Cell Movement - physiology; Computer Simulation; Dogs; Drosophila melanogaster; Epithelial Cells - physiology; Epithelium; Fluorescent Antibody Technique; Humanities and Social Sciences; In Vitro Techniques; Intravital Microscopy; Laser Therapy; Life Sciences; Madin Darby Canine Kidney Cells; Mathematics; Mechanics; Microsurgery; multidisciplinary; Numerical Analysis; Physics; Science; Science (multidisciplinary); Wound Healing - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8683

Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. Epithelial wound closure proceeds through both crawling into the wound and by constricting an actomyosin cable in a so-called purse-string mechanism. Here the authors show that the two mechanisms are mechanically coupled and the curvature of the wound regulates the overall dynamics of wound closure.