Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways

Steven S. An, Corin M. Pennella, Achuta Gonnabathula, Jianxin Chen, Ning Wang, Matthias Gaestel, Paul M. Hassoun, Jeffrey J. Fredberg, Usamah S. Kayyali

Research output: Contribution to journalArticle

Abstract

Hypoxia alters the barrier function of the endothelial cells that line the pulmonary vasculature, but underlying biophysical mechanisms remain unclear. Using rat pulmonary microvascular endothelial cells (RPMEC) in culture, we report herein changes in biophysical properties, both in space and in time, that occur in response to hypoxia. We address also the molecular basis of these changes. At the level of the single cell, we measured cell stiffness, the distribution of traction forces exerted by the cell on its substrate, and spontaneous nanoscale motions of microbeads tightly bound to the cytoskeleton (CSK). Hypoxia increased cell stiffness and traction forces by a mechanism that was dependent on the activation of Rho kinase. These changes were followed by p38-mediated decreases in spontaneous bead motions, indicating stabilization of local cellular-extracellular matrix (ECM) tethering interactions. Cells overexpressing phospho-mimicking small heat shock protein (HSP27-PM), a downstream effector of p38, exhibited decreases in spontaneous bead motions that correlated with increases in actin polymerization in these cells. Together, these findings suggest that hypoxia differentially regulates endothelial cell contraction and cellular-ECM adhesion.

Original languageEnglish (US)
Pages (from-to)C521-C530
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number3 58-3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Actin dynamics
  • Cytoskeleton
  • Endothelial barrier
  • Stiffness
  • Tensile stress

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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  • Cite this

    An, S. S., Pennella, C. M., Gonnabathula, A., Chen, J., Wang, N., Gaestel, M., Hassoun, P. M., Fredberg, J. J., & Kayyali, U. S. (2005). Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways. American Journal of Physiology - Cell Physiology, 289(3 58-3), C521-C530. https://doi.org/10.1152/ajpcell.00429.2004