Finite-element stress analysis of a multicomponent model of sheared andfocally-adhered endothelial cells.
Ferko,MC; Bhatnagar,A; Garcia,MB; Butler,PJ
Abstract Hemodynamic forces applied at the apical surface of vascular endothelialcells may be redistributed to and amplified at remote intracellular organelles and protein complexeswhere they are transduced to biochemical signals. In this study we sought to quantify the effectsof cellular material inhomogeneities and discrete attachment points on intracellular stressesresulting from physiological fluid flow. Steady-state shear- and magnetic bead-induced stress,strain, and displacement distributions were determined from finite-element stress analysis of acell-specific, multicomponent elastic continuum model developed from multimodal fluorescence imagesof confluent endothelial cell (EC) monolayers and their nuclei. Focal adhesion locations and areaswere determined from quantitative total internal reflection fluorescence microscopy and verifiedusing green fluorescence protein-focal adhesion kinase (GFP-FAK). The model predicts that shearstress 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 thehigh-modulus nucleus and near focal adhesions (FAs) and stress distributions depended on flowdirection. The presence of a 0.4 microm glycocalyx was predicted to increase intracellular stressesby approximately 2-fold. The model of magnetic bead twisting rheometry also predicted heterogeneousstress, strain, and displacement fields resulting from material heterogeneities and FAs. Thus, largedifferences in moduli between the nucleus and cytoplasm and the juxtaposition of constrainedregions (e.g. FAs) and unattached regions provide two mechanisms of stress amplification in shearedendothelial cells. Such phenomena may play a role in subcellular localization of earlymechanotransduction events.
Keywords Cell Adhesion; Endothelial Cells; Focal Adhesions; Mechanotransduction,Cellular
Annals of Biomedical Engineering
0090-6964, Volume 35, Issue 2, 2007, Pages 3-223
