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

• Type of Material: Article
• Authors: Melissa A. Kinney, Emory University; Rabbia Saeed, Emory University; Todd McDevitt, Emory University
• Language: English
• Date: 2014-03-06
• Publisher: Nature Publishing Groups
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Springer Nature Limited.
• Final Published Version (URL): http://dx.doi.org/10.1038/srep04290
• Title of Journal or Parent Work: Scientific Reports
• Volume: 4
• Issue: 1
• Start Page: 4290
• End Page: 4290
• Grant/Funding Information: M.A.K. is currently supported by an American Heart Association (AHA) Pre-Doctoral Fellowship and previously by an NSF Graduate Research Fellowship.; This work was supported by the National Institutes of Health (NIH R01 EB010061) and the National Science Foundation Emergent Behavior of Integrated Cellular Systems (EBICS) Science and Technology Center (CBET 093511).
• Keywords: Science & Technology; Substrate; Tissue; Adhesion; Gastrulation; Differentiation; Forces; Mesoderm; Primitive streak; Mechanical properties; Multidisciplinary Sciences; Zebrafish; Science & Technology - Other Topics
• Research Categories: Engineering, Biomedical; Chemistry, Biochemistry; Biology, Cell

Abstract

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.