4.7 Article

Mapping the dynamics of shear stress-induced structural changes in endothelial cells

期刊

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 293, 期 5, 页码 C1616-C1626

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00457.2006

关键词

mechanotransduction; cytoskeleton; extracellular matrix; focal adhesion

资金

  1. NHLBI NIH HHS [R01 HL071958, R01 HL071958-04, HL-071958] Funding Source: Medline
  2. NIGMS NIH HHS [GM-008715, T32 GM008715] Funding Source: Medline

向作者/读者索取更多资源

Hemodynamic shear stress regulates endothelial cell biochemical processes that govern cytoskeletal contractility, focal adhesion dynamics, and extracellular matrix (ECM) assembly. Since shear stress causes rapid strain focusing at discrete locations in the cytoskeleton, we hypothesized that shear stress coordinately alters structural dynamics in the cytoskeleton, focal adhesion sites, and ECM on a time scale of minutes. Using multiwavelength four-dimensional fluorescence microscopy, we measured the displacement of rhodamine-fibronectin and green fluorescent protein-labeled actin, vimentin, paxillin, and/or vinculin in aortic endothelial cells before and after onset of steady unidirectional shear stress. In the cytoskeleton, the onset of shear stress increased actin polymerization into lamellipodia, altered the angle of lateral displacement of actin stress fibers and vimentin filaments, and decreased centripetal remodeling of actin stress fibers in subconfluent and confluent cell layers. Shear stress induced the formation of new focal complexes and reduced the centripetal remodeling of focal adhesions in regions of new actin polymerization. The structural dynamics of focal adhesions and the fibronectin matrix varied with cell density. In subconfluent cell layers, shear stress onset decreased the displacement of focal adhesions and fibronectin fibrils. In confluent monolayers, the direction of fibronectin and focal adhesion displacement shifted significantly toward the downstream direction within 1 min after onset of shear stress. These spatially coordinated rapid changes in the structural dynamics of cytoskeleton, focal adhesions, and ECM are consistent with focusing of mechanical stress and/or strain near major sites of shear stress-mediated mechanotransduction.

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