Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: Atomic force microscopy force mapping of pulmonary endothelial monolayer

Anna A. Birukova, Fernando T. Arce, Nurgul Moldobaeva, Steven M. Dudek, Joe G.N. Garcia, Ratnesh Lal, Konstantin G. Birukov

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Actomyosin contraction directly regulates endothelial cell (EC) permeability, but intracellular redistribution of cytoskeletal tension associated with EC permeability is poorly understood. We used atomic force microscopy (AFM), EC permeability assays, and fluorescence microscopy to link barrier regulation, cell remodeling, and cytoskeletal mechanical properties in EC treated with barrier-protective as well as barrier-disruptive agonists. Thrombin, vascular endothelial growth factor, and hydrogen peroxide increased EC permeability, disrupted cell junctions, and induced stress fiber formation. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, hepatocyte growth factor, and iloprost tightened EC barriers, enhanced peripheral actin cytoskeleton and adherens junctions, and abolished thrombin-induced permeability and EC remodeling. AFM force mapping and imaging showed differential distribution of cell stiffness: barrier-disruptive agonists increased stiffness in the central region, and barrier-protective agents decreased stiffness in the center and increased it at the periphery. Attenuation of thrombin-induced permeability correlates well with stiffness changes from the cell center to periphery. These results directly link for the first time the patterns of cell stiffness with specific EC permeability responses.

Original languageEnglish (US)
Pages (from-to)30-41
Number of pages12
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume5
Issue number1
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

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Keywords

  • Actin cytoskeleton
  • Agonists
  • Force mapping
  • Permeability
  • Pulmonary endothelium

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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