Journal
CIRCULATION RESEARCH
Volume 86, Issue 7, Pages 745-752Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.86.7.745
Keywords
mechanotransduction; endothelium; green fluorescent protein
Funding
- NHLBI NIH HHS [HL10058, HL36049] Funding Source: Medline
- NIGMS NIH HHS [GM36806] Funding Source: Medline
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Hemodynamic shear stress at the endothelial cell surface induces acute and chronic intracellular responses that regulate vessel wall biology. The cytoskeleton is implicated by acting both as a direct connector to local surface deformation and as a distribution network for mechanical forces throughout the cell; however, direct observation and measurement of its position during flow have only recently become possible. In this study, we directly demonstrate rapid deformation of the intermediate filament (IF) network in living endothelial cells subjected to changes in hemodynamic shear stress. Time-lapse optical sectioning and deconvolution microscopy were performed within the first 3 minutes after the introduction of flow (shear stress, 12 dyn/cm(2)). Spatial and temporal dynamics of green fluorescent protein-vimentin Ifs in confluent endothelial cells were analyzed. The imposition of shear stress significantly increased the variability of IF movement throughout the cell in the x-, y-, and z-directions compared with the constitutive dynamics noted in the absence of flow. Acute polymerization and depolymerization of the IF network were absent. The magnitude and direction of flow-induced LF displacement were heterogeneous at the subcellular level. These qualitative and quantitative data demonstrate that shear stress acting at the luminal surface of the endothelium results in rapid deformation of a stable IF network.
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