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Regulation of the Micromechanical Properties of Pulmonary Endothelium by S1P and Thrombin: Role of Cortactin

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

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

Topics: Cell Biophysics
Publisher: The Biophysical Society
OAI identifier: oai:pubmedcentral.nih.gov:2440433
Provided by: PubMed Central
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