Mesenchymal morphogenesis of embryonic stem cells dynamically modulates the biophysical microtissue niche

Sci Rep. 2014 Mar 6;4:4290. doi: 10.1038/srep04290.


Stem cell fate and function are dynamically modulated by the interdependent relationships between biochemical and biophysical signals constituting the local 3D microenvironment. While approaches to recapitulate the stem cell niche have been explored for directing stem cell differentiation, a quantitative relationship between embryonic stem cell (ESC) morphogenesis and intrinsic biophysical cues within three-dimensional microtissues has not been established. In this study, we demonstrate that mesenchymal embryonic microtissues induced by BMP4 exhibited increased stiffness and viscosity accompanying differentiation, with cytoskeletal tension significantly contributing to multicellular stiffness. Perturbation of the cytoskeleton during ESC differentiation led to modulation of the biomechanical and gene expression profiles, with the resulting cell phenotype and biophysical properties being highly correlated by multivariate analyses. Together, this study elucidates the dynamics of biophysical and biochemical signatures within embryonic microenvironments, with broad implications for monitoring tissue dynamics, modeling pathophysiological and embryonic morphogenesis and directing stem cell patterning and differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Cell Culture Techniques
  • Cell Differentiation*
  • Cell Line
  • Cytoskeleton / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Mesoderm / embryology*
  • Mice
  • Morphogenesis*
  • Multivariate Analysis
  • Phenotype


  • Bone Morphogenetic Protein 4