Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors

Kshitiz, Maimon E. Hubbi, Eun Hyun Ahn, John Downey, Junaid Afzal, Deok Ho Kim, Sergio Rey, Connie Chang, Arnab Kundu, Gregg L. Semenza, Roselle M. Abraham, Andre Levchenko

Research output: Contribution to journalArticle

Abstract

Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood.We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase- activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation.

Original languageEnglish (US)
Article numberra41
JournalScience signaling
Volume5
Issue number227
DOIs
StatePublished - Jun 5 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kshitiz, Hubbi, M. E., Ahn, E. H., Downey, J., Afzal, J., Kim, D. H., Rey, S., Chang, C., Kundu, A., Semenza, G. L., Abraham, R. M., & Levchenko, A. (2012). Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. Science signaling, 5(227), [ra41]. https://doi.org/10.1126/scisignal.2003002