Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: Role of cortactin

Fernando Terán Arce, Jenny L. Whitlock, Anna A. Birukova, Konstantin G. Birukov, Morton F. Arnsdorf, Ratnesh Lal, Joe G.N. Garcia, Steven M. Dudek

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Disruption of pulmonary endothelial cell (EC) barrier function is a critical pathophysiologic event in highly morbid inflammatory conditions such as sepsis and acute respiratory disease stress syndrome. Actin cytoskeleton, an essential regulator of endothelial permeability, is a dynamic structure whose stimuli-induced rearrangement is linked to barrier modulation. Here, we used atomic force microscopy to characterize structural and mechanical changes in the F-actin cytoskeleton of cultured human pulmonary artery EC in response to both barrier-enhancing (induced by sphingosine 1-phosphate (S1P)) and barrier-disrupting (induced by thrombin) conditions. Atomic force microscopy elasticity measurements show differential effects: for the barrier protecting molecule S1P, the elastic modulus was elevated significantly on the periphery; for the barrier-disrupting molecule thrombin, on the other hand, it was elevated significantly in the central region of the cell. The force and elasticity maps correlate with F-actin rearrangements as identified by immunofluorescence analysis. Significantly, reduced expression (via siRNA) of cortactin, an actin-binding protein essential to EC barrier regulation, resulted in a shift in the S1P-mediated elasticity pattern to more closely resemble control, unstimulated endothelium.

Original languageEnglish (US)
Pages (from-to)886-894
Number of pages9
JournalBiophysical Journal
Volume95
Issue number2
DOIs
StatePublished - Jul 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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    Arce, F. T., Whitlock, J. L., Birukova, A. A., Birukov, K. G., Arnsdorf, M. F., Lal, R., Garcia, J. G. N., & Dudek, S. M. (2008). Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: Role of cortactin. Biophysical Journal, 95(2), 886-894. https://doi.org/10.1529/biophysj.107.127167