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 GN Garcia, Steven M. Dudek

Research output: Contribution to journalArticle

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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

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Cortactin
Elasticity
Thrombin
Endothelium
Endothelial Cells
Atomic Force Microscopy
Actin Cytoskeleton
Lung
Actins
Microfilament Proteins
Elastic Modulus
Acute Disease
Small Interfering RNA
Pulmonary Artery
Fluorescent Antibody Technique
Permeability
Sepsis
sphingosine 1-phosphate

ASJC Scopus subject areas

  • Biophysics

Cite this

Arce, F. T., Whitlock, J. L., Birukova, A. A., Birukov, K. G., Arnsdorf, M. F., Lal, R., ... 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

Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin : Role of cortactin. / Arce, Fernando Terán; Whitlock, Jenny L.; Birukova, Anna A.; Birukov, Konstantin G.; Arnsdorf, Morton F.; Lal, Ratnesh; Garcia, Joe GN; Dudek, Steven M.

In: Biophysical Journal, Vol. 95, No. 2, 15.07.2008, p. 886-894.

Research output: Contribution to journalArticle

Arce, FT, Whitlock, JL, Birukova, AA, Birukov, KG, Arnsdorf, MF, Lal, R, Garcia, JGN & Dudek, SM 2008, 'Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: Role of cortactin', Biophysical Journal, vol. 95, no. 2, pp. 886-894. https://doi.org/10.1529/biophysj.107.127167
Arce, Fernando Terán ; Whitlock, Jenny L. ; Birukova, Anna A. ; Birukov, Konstantin G. ; Arnsdorf, Morton F. ; Lal, Ratnesh ; Garcia, Joe GN ; Dudek, Steven M. / Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin : Role of cortactin. In: Biophysical Journal. 2008 ; Vol. 95, No. 2. pp. 886-894.
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