Authors: Michael C Ferko Amit Bhatnagar Mariana B Garcia Peter J Butler
Publish Date: 2006/12/12
Volume: 35, Issue: 2, Pages: 208-223
Abstract
Hemodynamic forces applied at the apical surface of vascular endothelial cells may be redistributed to and amplified at remote intracellular organelles and protein complexes where they are transduced to biochemical signals In this study we sought to quantify the effects of cellular material inhomogeneities and discrete attachment points on intracellular stresses resulting from physiological fluid flow Steadystate shear and magnetic beadinduced stress strain and displacement distributions were determined from finiteelement stress analysis of a cellspecific multicomponent elastic continuum model developed from multimodal fluorescence images of confluent endothelial cell EC monolayers and their nuclei Focal adhesion locations and areas were determined from quantitative total internal reflection fluorescence microscopy and verified using green fluorescence protein–focal adhesion kinase GFP–FAK The model predicts that shear stress induces small heterogeneous deformations of the endothelial cell cytoplasm on the order of 100 nm However strain and stress were amplified 10–100fold over apical values in and around the highmodulus nucleus and near focal adhesions FAs and stress distributions depended on flow direction The presence of a 04 μm glycocalyx was predicted to increase intracellular stresses by ∼2fold The model of magnetic bead twisting rheometry also predicted heterogeneous stress strain and displacement fields resulting from material heterogeneities and FAs Thus large differences in moduli between the nucleus and cytoplasm and the juxtaposition of constrained regions eg FAs and unattached regions provide two mechanisms of stress amplification in sheared endothelial cells Such phenomena may play a role in subcellular localization of early mechanotransduction eventsThis work was supported in part by a grant to PJB from the National Heart Lung and Blood Institute R01 HL 07754201A1 by a National Science Foundation Career Award to PJB BES 0238910 and by a seed grant from the Center for Optical Technologies Bethlehem PA GFP–FAK was a gift from Song Li PhD University of California Berkeley MBG was supported by the Penn State Biomaterials and Bionanotechnology Summer Institute NIBIBNSF EEC 0234026
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