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Finite-Element Stress Analysis of a Multicomponent Model of Sheared and Focally-Adhered Endothelial Cells

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An Erratum to this article was published on 22 March 2007

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. Steady-state shear- and magnetic bead-induced stress, strain, and displacement distributions were determined from finite-element stress analysis of a cell-specific, 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 10–100-fold over apical values in and around the high-modulus nucleus and near focal adhesions (FAs) and stress distributions depended on flow direction. The presence of a 0.4 μm glycocalyx was predicted to increase intracellular stresses by ∼2-fold. 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 (e.g. 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 events.

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Acknowledgments

This work was supported in part by a grant to PJB from the National Heart Lung and Blood Institute (R01 HL 077542-01A1), 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, Ph.D., University of California, Berkeley. MBG was supported by the Penn State Biomaterials and Bionanotechnology Summer Institute (NIBIB-NSF EEC 0234026).

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  1. Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, University Park, PA, 16802, USA

    Michael C. Ferko, Amit Bhatnagar, Mariana B. Garcia & Peter J. Butler

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  1. Michael C. Ferko
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  2. Amit Bhatnagar
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  3. Mariana B. Garcia
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Correspondence to Peter J. Butler.

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An erratum to this article is available at http://dx.doi.org/10.1007/s10439-007-9280-3.

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Ferko, M.C., Bhatnagar, A., Garcia, M.B. et al. Finite-Element Stress Analysis of a Multicomponent Model of Sheared and Focally-Adhered Endothelial Cells. Ann Biomed Eng 35, 208–223 (2007). https://doi.org/10.1007/s10439-006-9223-4

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