Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells

Hu, Shaohua; Chen, Jianxin; Fabry, Ben; Numaguchi, Yasushi; Gouldstone, Andrew; Ingber, Donald E.; Fredberg, Jeffrey J.; Butler, James P.; Wang, Ning

doi:10.1152/ajpcell.00159.2003

Cited by 228 publications

(241 citation statements)

References 34 publications

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“…The simulation demonstrated that anisotropic tension supported by discrete focal contacts could produce the spatial distribution of stress fibers. This concept is consistent with a tensegrity model known as a conceptual model of mechanical coordination between the parts of a cell and the cell as a whole [38][39][40].…”

Section: Discussionsupporting

confidence: 78%

Contribution of cellular contractility to spatial and temporal variations in cellular stiffness

Nagayama

Haga

Takahashi

et al. 2004

Experimental Cell Research

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Scanning probe microscopy and immunofluorescence observations indicated that cellular stiffness was attributed to a contractile network structure consisting of stress fibers. We measured temporal variations in cellular stiffness when cellular contractility was regulated by dosing with lysophosphatidic acid or Y-27632. This experiment reveals a clear relation between cellular stiffness and contractility: Increases in contractility cause cells to stiffen. On the other hand, decreases in contractility reduce cellular stiffness. In both cases, not only the stiffness of the stress fibers but also that of the whole of the cell varies. Immunofluorescence observations of myosin II and vinculin indicated that the stiffness variations induced by the regulation of cellular contractility were mainly due to rearrangements of the contractile actin network on the dorsal surface. Taken together, our findings provide evidence that the actin cytoskeletal network and its contractility features provide and modulate the mechanical stability of adherent cells.

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Section: Discussionsupporting

confidence: 78%

Contribution of cellular contractility to spatial and temporal variations in cellular stiffness

Nagayama

Haga

Takahashi

et al. 2004

Experimental Cell Research

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“…The only experimental data available that demonstrates stress focusing is by Hu et al who analyzed mitochondria displacements in response to bead twisting. 25 In order to test whether our model could predict experimentallyobserved stress focusing, we modified our finite element model to simulate bead twisting of 20° around the horizontal axis as in 35 and predicted the resultant deformation and stress distributions in the EC cytoplasm at 1 μm from the cell base. In this case fluid flow was not simulated over the cell surface.…”

Section: Determination Of Stress Focusing In Response To Shear Stressmentioning

confidence: 99%

“…In support of decentralized forces, shear stress caused deformation of intermediate filaments, 23 strain focusing at focal adhesions (FAs) 24 and stress focusing in the cell interior. 25 But shear stress also activates PECAM-1, a protein in cell junctions near the cell surface. This activation may lead to production of a diffusible factor which induces activation of integrins in FAs, where stresses may be concentrated.…”

Section: Introductionmentioning

confidence: 99%

“…In order to compare our model with available experimental data, we computed stresses and displacements at 1 μm above the cell base in response to magnetic bead twisting as in Ref. 25 In the discussion, we estimate the degree of stress amplification due to the presence of an intact glycocalyx. This type of cell-specific modeling based on experimentally-determined topographies and boundary conditions may help identify potential sites of force-induced potentiation and directional-biasing of cell signaling.…”

Section: Introductionmentioning

confidence: 99%

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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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“…12,43,113 Furthermore, studies of stress and strain on cells have increased the understanding of mechanics with respect to intracellular behavior involving the cytoskeleton. 35,39 From a biochemical perspective, local modulation of integrin receptors affects cell behavior because applying mechanical stresses alters the expression of cyclic AMP as well as induces local recruitment of mRNA and ribosomes to focal adhesions. 10,65 Membrane receptor signaling and gene transcription are activated in a force-dependent manner by applying magnetic twisting forces to these receptors via ferromagnetic beads coated with specific receptor ligands (Fig.…”

Section: Mechanotransductionmentioning

confidence: 99%

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

LeDuc

Bellin

2006

Ann Biomed Eng

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Abstract-Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano-and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

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Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells

Cited by 228 publications

References 34 publications

Contribution of cellular contractility to spatial and temporal variations in cellular stiffness

Contribution of cellular contractility to spatial and temporal variations in cellular stiffness

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

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

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