Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 1 , Pages 30-41, March 2009

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

  • Anna A. Birukova, MD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • These authors contributed equally in this study.
    • ,
  • Fernando T. Arce, PhD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • Department of Medicine, Center for Nanomedicine, University of Chicago, Chicago, Illinois, USA
    • These authors contributed equally in this study.
    • ,
  • Nurgul Moldobaeva, BS

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • ,
  • Steven M. Dudek, MD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • ,
  • Joe G.N. Garcia, MD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • ,
  • Ratnesh Lal, PhD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • Department of Medicine, Center for Nanomedicine, University of Chicago, Chicago, Illinois, USA
    • ,
  • Konstantin G. Birukov, MD, PhD

      Affiliations

    • Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Care Medicine University of Chicago, Chicago, Illinois, USA
    • Corresponding Author InformationCorresponding author. Division of Biomedical Sciences, Department of Medicine, Section of Pulmonary and Critical Medicine, University of Chicago, Chicago, IL 60637, USA.

Received 2 January 2008; accepted 30 July 2008. published online 29 September 2008.

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.

Keywords: Pulmonary endothelium, Permeability, Agonists, Actin cytoskeleton, Force mapping

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 This work was supported by National Heart, Lung, and Blood Institutes grants HL076259, HL075349, and HL58064, the American Lung Association Career Investigator Grant (K.G.B.); National Scientist Developing Grant from the American Heart Association (A.A.B.), the American Lung Association Biomedical Research Grant (A.A.B.); and Department of Medicine Developmental Fund (R.L., F.T.A.).

PII: S1549-9634(08)00117-2

doi:10.1016/j.nano.2008.07.002

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 1 , Pages 30-41, March 2009

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