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Cellular forces and matrix assembly coordinate fibrous tissue repair

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  • Mahmut Selman Sakar

    (Institute of Robotics and Intelligent Systems, Eidgenössische Technische Hochschule Zürich
    Present address: Institute of Mechanical Engineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.)

  • Jeroen Eyckmans

    (Boston University
    Wyss Institute for Biologically Inspired Engineering, Harvard University)

  • Roel Pieters

    (Institute of Robotics and Intelligent Systems, Eidgenössische Technische Hochschule Zürich)

  • Daniel Eberli

    (Laboratory for Urologic Tissue Engineering and Stem Cell Therapy, University Hospital)

  • Bradley J. Nelson

    (Institute of Robotics and Intelligent Systems, Eidgenössische Technische Hochschule Zürich)

  • Christopher S. Chen

    (Boston University
    Wyss Institute for Biologically Inspired Engineering, Harvard University)

Abstract

Planar 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 architecture.

Suggested Citation

  • Mahmut 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, Nature, vol. 7(1), pages 1-8, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11036
    DOI: 10.1038/ncomms11036
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