Is cytoskeletal tension a major determinant of  cell deformability in adherent endothelial cells?

Pourati, Jacob; Maniotis, Andrew J.; Spiegel, David A.; Schaffer, Jonathan; Butler, James P.; Fredberg, Jeffrey J.; Ingber, Donald E.; Stamenovic, Dimitrijie; Wang, Ning

doi:10.1152/ajpcell.1998.274.5.c1283

Cited by 206 publications

(191 citation statements)

References 29 publications

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“…A disruption of the F-actin fiber network as described after cytochalasin D treatment was not observed. Together with the knowledge that the actin cytoskeleton determines the mechanical properties of cells (Byfield et al, 2009;Pourati et al, 1998) we conclude that the observed reorganization of the actin cytoskeleton upon adrenergic stimulation of osteoblasts with clenbuterol leads to the apparent cell stiffening.…”

Section: Discussionsupporting

confidence: 61%

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Lee-Thedieck

Rauch

Fiammengo

et al. 2012

Journal of Cell Science

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SummaryIn the bone marrow, hematopoietic stem cells (HSCs) reside in endosteal and vascular niches. The interactions with the niches are essential for the maintenance of HSC number and properties. Although the molecular nature of these interactions is well understood, little is known about the role of physical parameters such as matrix elasticity. Osteoblasts, the major cellular component of the endosteal HSC niche, flatten during HSC mobilization. We show that this process is accompanied by osteoblast stiffening, demonstrating that not only biochemical signals but also mechanical properties of the niche are modulated. HSCs react to stiffer substrates with increased cell adhesion and migration, which could facilitate the exit of HSCs from the niche. These results indicate that matrix elasticity is an important factor in regulating the retention of HSCs in the endosteal niche and should be considered in attempts to propagate HSCs in vitro for clinical applications.

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Section: Discussionsupporting

confidence: 61%

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Lee-Thedieck

Rauch

Fiammengo

et al. 2012

Journal of Cell Science

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“…Pourati and colleagues demonstrated that prestress increases endothelial cell stiffness in response to eternally applied forces. 40 In their study, stiffness increased by about 10 and 25% in response to 2.5 and 5% strain applied at the surface, respectively. These strains are much larger than the surface strains predicted in our model in response to 10 dynes/cm 2 surface shear stress.…”

Section: Prestress In Cellsmentioning

confidence: 90%

“…Endothelial cells exhibit contractility under static conditions 40 suggesting that cells are stressed internally. Due to the large number of filaments in the cell, it would be difficult to account for prestress in each filament and incorporate it into a holistic model.…”

Section: Prestress In Cellsmentioning

confidence: 99%

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

et al. 2007

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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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“…Cell stiffness, which is closely related to cytoskeletal tension (20), has been shown to increase in response to mechanical stretch and cell contraction (20,21). These results suggest that each of these stimuli can generate tension in stress fibers.…”

mentioning

confidence: 92%

Cooperative effects of Rho and mechanical stretch on stress fiber organization

Kaunas

Nguyen

Usami

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

375

417

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The small GTPase Rho regulates the formation of actin stress fibers in adherent cells through activation of its effector proteins Rhokinase and mDia. We found in bovine aortic endothelial cells that inhibitions of Rho, Rho-kinase, and mDia (with C3, Y27632, and F1F2⌬1, respectively) suppressed stress fiber formation, but fibers appeared after 10% cyclic uniaxial stretch (1-Hz frequency). In contrast to the predominately perpendicular alignment of stress fibers to the stretch direction in normal cells, the stress fibers in cells with Rho pathway inhibition became oriented parallel to the stretch direction. In cells with normal Rho activity, the extent of perpendicular orientation of stress fibers depended on the magnitude of stretch. Expressing active RhoV14 plasmid in these cells enhanced the stretch-induced stress fiber orientation by an extent equivalent to an additional Ϸ3% stretch. This augmentation of the stretch-induced perpendicular orientation by RhoV14 was blocked by Y27632 and by F1F2⌬1. Thus, the activity of the Rho pathway plays a critical role in determining both the direction and extent of stretch-induced stress fiber orientation in bovine aortic endothelial cells. Our results demonstrate that the stretch-induced stress fiber orientation is a function of the interplay between Rho pathway activity and the magnitude of stretching.cytoskeletal dynamics ͉ endothelial cells ͉ mechanotransduction ͉ Rho-kinase T he tension generated by contraction of adherent cells against their underlying surface results in an internal stress field that depends on the organization of the cytoskeleton and the associated adhesive contacts (see ref. 1 for review). Intracellular forces have an important role in cellular functions such as migration, proliferation, apoptosis, differentiation, and gene expression (see refs. 2-4 for reviews). Actin stress fibers, which are formed in response to cell contraction (5), consist of bundles of actin microfilaments cross-linked by ␣-actinin, myosin, myosin light-chain, tropomyosin, and other proteins arranged in a manner similar to that in muscle sarcomeres (6). Stress fibers represent the main contractile apparatus in non-muscle cells (7) and are the primary structures associated with intracellular tension. Stress fibers terminate at focal adhesions, which attach the cell to the extracellular matrix (8). Isometric contraction of a cell would result in tension development in the stress fibers, which are anchored at their ends.The activation of the small GTPase Rho leads to stress fiber assembly (9) and cell contraction by means of myosin light chain phosphorylation (5), which is regulated by Rho-kinase, a downstream effector of Rho (10). mDia, another Rho effector, is also involved in stress fiber formation downstream of Rho activation (11), possibly by regulating actin polymerization and focal adhesion turnover through its association with profilin (12, 13) and src-tyrosine-kinase (14), respectively.Cyclic uniaxial stretch induces the orientation of stress fibers in endothelial cells ...

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Is cytoskeletal tension a major determinant of cell deformability in adherent endothelial cells?

Cited by 206 publications

References 29 publications

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

Impact of substrate elasticity on human hematopoietic stem and progenitor cell adhesion and motility

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

Cooperative effects of Rho and mechanical stretch on stress fiber organization

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