Sakar, Mahmut SelmanEyckmans, JeroenPieters, RoelEberli, DanielNelson, Bradley J.Chen, Christopher S.2020-04-142020-04-142016-03-01Mahmut Selman Sakar, Jeroen Eyckmans, Roel Pieters, Daniel Eberli, Bradley J Nelson, Christopher S Chen. 2016. "Cellular forces and matrix assembly coordinate fibrous tissue repair." NATURE COMMUNICATIONS, Volume 7, 8 pp. https://doi.org/10.1038/ncomms110362041-1723https://hdl.handle.net/2144/40143Planar in vitro models have been invaluable tools to identify the mechanical basis of wound closure. Although these models may recapitulate closure dynamics of epithelial cell sheets, they fail to capture how a wounded fibrous tissue rebuilds its 3D architecture. Here we develop a 3D biomimetic model for soft tissue repair and demonstrate that fibroblasts ensconced in a collagen matrix rapidly close microsurgically induced defects within 24 h. Traction force microscopy and time-lapse imaging reveal that closure of gaps begins with contractility-mediated whole-tissue deformations. Subsequently, tangentially migrating fibroblasts along the wound edge tow and assemble a progressively thickening fibronectin template inside the gap that provide the substrate for cells to complete closure. Unlike previously reported mechanisms based on lamellipodial protrusions and purse-string contraction, our data reveal a mode of stromal closure in which coordination of tissue-scale deformations, matrix assembly and cell migration act together to restore 3D tissue architecture8 pagesen-USThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0Science & technologyMultidisciplinary sciencesNeural-tube closureIn-vitroDrosophila embryosEpithelial closureDorsal closureMorphogenesisMigrationMechanicsDynamicsModelAnimalsCadherinsCell culture techniquesCell movementCollagen type IFibroblastsFibronectinsGene knockdown techniquesImmunohistochemistryMiceMicroscopy, atomic forceMicrosurgeryModels, theoreticalNIH 3T3 cellsSoft tissue injuriesTime-lapse imagingWound healingArticle10.1038/ncomms110360000-0003-1475-8149 (Eyckmans, Jeroen)0000-0003-2445-8449 (Chen, Christopher S)174532