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 journalArticlepeer-review

53 Scopus citations


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
Issue number2
StatePublished - Jul 15 2008

ASJC Scopus subject areas

  • Biophysics


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