Spatial mapping of tissue properties in vivo reveals a 3D stiffness gradient in the mouse limb bud

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  • Min Zhu
    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada;
  • Hirotaka Tao
    Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 0A4, Canada;
  • Mohammad Samani
    Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 0A4, Canada;
  • Mengxi Luo
    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada;
  • Xian Wang
    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada;
  • Sevan Hopyan
    Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON M5G 0A4, Canada;
  • Yu Sun
    Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8, Canada;

説明

<jats:p> Numerous hypotheses invoke tissue stiffness as a key parameter that regulates morphogenesis and disease progression. However, current methods are insufficient to test hypotheses that concern physical properties deep in living tissues. Here we introduce, validate, and apply a magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate an organ-stage mouse embryo under live conditions. The method allows rapid, nontoxic measurement of the three-dimensional (3D) spatial distribution of viscoelastic properties within mesenchyme and epithelia. Using the device, we identify an anteriorly biased mesodermal stiffness gradient along which cells move to shape the early limb bud. The stiffness gradient corresponds to a <jats:italic>Wnt5a</jats:italic> -dependent domain of fibronectin expression, raising the possibility that durotaxis underlies cell movements. Three-dimensional stiffness mapping enables the generation of hypotheses and potentially the rigorous testing of mechanisms of development and disease. </jats:p>

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