Modeling of Stress Fiber Organization in Cyclically Stretched Cells

2007 ◽  
Author(s):  
Zhensong Wei ◽  
Vikram S. Deshpande ◽  
Robert M. McMeeking ◽  
Anthony G. Evans
Keyword(s):  
Stress Fiber ◽  
Stress Fibers ◽  
Parameter Study ◽  
Transverse Strain ◽  
Fiber Alignment ◽  
Cyclic Stretching ◽  
Cycling Frequency ◽  
Strain Magnitude ◽  
Distribution Of Stress ◽  
Fiber Organization

Numerical simulations that incorporate a bio-chemo-mechanical model for the contractility of the cytoskeleton have been used to rationalize the following observations. Uniaxial cyclic stretching of cells causes stress fibers to align perpendicular to the stretch direction, with degree of alignment dependent on the stretch strain magnitude, as well as the frequency and the transverse strain. Conversely, equibiaxial cyclic stretching induces a uniform distribution of stress fiber orientations. Demonstrations that the model successfully predicts the alignments found experimentally are followed by a parameter study to investigate the influence of the straining frequency and the transverse contraction of the substrate. The primary predictions are as follows. The fiber alignment increases with increasing cycling frequency. Transverse contraction of the substrate causes the stress fibers to organize into two symmetrical orientations with respect to the primary stretch direction.

Analysis and Interpretation of Stress Fiber Organization in Cells Subject to Cyclic Stretch

2008 ◽  
Vol 130 (3) ◽  
Author(s):  
Zhensong Wei ◽  
Vikram S. Deshpande ◽  
Robert M. McMeeking ◽  
Anthony G. Evans
Keyword(s):  
Rate Sensitivity ◽  
Intrinsic Rate ◽  
Stress Fiber ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Parameter Study ◽  
Cyclic Stretching ◽  
Cycling Frequency ◽  
Key Variables ◽  
Distribution Of Stress

Numerical simulations that incorporate a biochemomechanical model for the contractility of the cytoskeleton have been used to rationalize the following observations. Uniaxial cyclic stretching of cells causes stress fibers to align perpendicular to the stretch direction, with degree of alignment dependent on the stretch strain magnitude, as well as the frequency and the transverse contraction of the substrate. Conversely, equibiaxial cyclic stretching induces a uniform distribution of stress fiber orientations. Demonstrations that the model successfully predicts the alignments experimentally found are followed by a parameter study to investigate the influence of a range of key variables including the stretch magnitude, the intrinsic rate sensitivity of the stress fibers, the straining frequency, and the transverse contraction of the substrate. The primary predictions are as follows. The rate sensitivity has a strong influence on alignment, equivalent to that attained by a few percent of additional stretch. The fiber alignment increases with increasing cycling frequency. Transverse contraction of the substrate causes the stress fibers to organize into two symmetrical orientations with respect to the primary stretch direction.

Comparison of the Effects of Cyclic Stretching and Compression on Endothelial Cell Morphological Responses

2004 ◽  
Vol 126 (5) ◽  
pp. 545-551 ◽  
Author(s):  
Jeremiah J. Wille ◽  
Christina M. Ambrosi ◽  
Frank C-P Yin
Keyword(s):  
Stress Fiber ◽  
Stress Fibers ◽  
Cell Orientation ◽  
Aortic Endothelial Cells ◽  
Cyclic Stretching ◽  
Rate Dependent ◽  
Pure Compression ◽  
Parallel Arrays ◽  
Human Aortic Endothelial Cells ◽  
Silicone Membranes

Recent results demonstrate the exquisite sensitivity of cell orientation responses to the pattern of imposed deformation. Cells undergoing pure in-plane uniaxial stretching orient differently than cells that are simply elongated—likely because the latter stimulus produces simultaneous compression in the unstretched direction. It is not known, however, if cells respond differently to pure stretching than to pure compression. This study was performed to address this issue. Human aortic endothelial cells were seeded on deformable silicone membranes and subjected to various magnitudes and rates of pure stretching or compression. The cell orientation and cytoskeletal stress fiber organization responses were examined. Both stretching and compression resulted in magnitude-dependent but not rate-dependent orientation responses away from the deforming direction. Compression produced a slower temporal response than stretching. However, stress fiber reorganization responses–early disruption followed by reassembly into parallel arrays along the cells’ long axes were similar between the two stimuli. Moreover, the cell orientation and stress fiber responses appeared to be uncoupled since disruption of stress fibers was not required for the cell orientation. Moreover, parallel actin stress fibers were observed at oblique angles to the deforming direction indicating that stress fibers can reassemble when undergoing deformation.

On the Intracellullar Memory of Stress Fiber Orientation: Effects of Microtubules and Focal Adhesions on the Repolymerization Process of Stress Fibers

2008 ◽  
Author(s):  
Yunfeng Yang ◽  
Kazuaki Nagayama ◽  
Takeo Matsumoto
Keyword(s):  
Fiber Orientation ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Cellular Functions ◽  
Division 1 ◽  
Key Features ◽  
Strain Magnitude

Stress fibers (SFs) play essential roles in various cellular functions such as cell movement, shape maintenance and cell division [1]. One of their key features is that they dynamically change their structures in response to mechanical environment to which they are exposed [2]. For example, cultured endothelial cells exposed to cyclic stretch preferentially reorganize their actin stress fibers to the direction in which the strain magnitude of the fibers become minimum [3].

scholarly journals Expression and intracellular distribution of stress fibers in aortic endothelium.

1986 ◽  
Vol 103 (1) ◽  
pp. 63-70 ◽  
Author(s):  
G E White ◽  
K Fujiwara
Keyword(s):  
Endothelial Cells ◽  
Age Groups ◽  
Stress Fiber ◽  
Intracellular Distribution ◽  
Stress Fibers ◽  
Shear Stresses ◽  
Hypertensive Rats ◽  
Fluid Shear ◽  
Aortic Endothelium ◽  
Distribution Of Stress

Immunofluorescence microscopy was used to determine the number of endothelial cells with stress fibers for three age groups, and for three distinct anatomical locations within the descending thoracic aorta of both normotensive and spontaneously hypertensive rats. For each age group examined, hypertensive rats consistently demonstrated greater stress fiber expression than did normotensive rats. Neither age nor blood pressure was the predominant influence on stress fiber expression in aortic endothelium. In the normotensive rats, stress fiber expression remained unchanged for all age groups examined. For both strains, however, more endothelial cells with stress fibers were found in those regions where fluid shear stresses are expected to be high, when compared with those regions where the fluid shear stresses are expected to be low. This observation suggests that anatomical location, with its implied differences in fluid shear stress levels, is a major influence on stress fiber expression within this tissue. Electron microscopy was used to determine the intracellular distribution of stress fibers for both strains. Most stress fibers in both strains were located in the abluminal portion of the endothelial cells. This result is consistent with a role for stress fibers in cellular adhesion. However, the hypertensive rats had a higher proportion of stress fibers in the luminal portion of their cytoplasm than the normotensive rats. This increased presence of stress fibers in the luminal portion of the cell may be important in maintaining the structural integrity of the endothelial cell in the face of elevated hemodynamic forces in situ.

scholarly journals Mechanoadaptive organization of stress fiber subtypes in epithelial cells under cyclic stretches and stretch release

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amir Roshanzadeh ◽  
Tham Thi Nguyen ◽  
Khoa Dang Nguyen ◽  
Dong-Su Kim ◽  
Bong-Kee Lee ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Stability ◽  
Myosin Ii ◽  
Mechanical Stretch ◽  
Stress Fiber ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Strain Magnitude ◽  
Additional Formation ◽  
Strain Dependent

Abstract Cyclic stretch applied to cells induces the reorganization of stress fibers. However, the correlation between the reorganization of stress fiber subtypes and strain-dependent responses of the cytoplasm and nucleus has remained unclear. Here, we investigated the dynamic involvement of stress fiber subtypes in the orientation and elongation of cyclically stretched epithelial cells. We applied uniaxial cyclic stretches at 5%, 10%, and 15% strains to cells followed by the release of the mechanical stretch. Dorsal, transverse arcs, and peripheral stress fibers were mainly involved in the cytoplasm responses whereas perinuclear cap fibers were associated with the reorientation and elongation of the nucleus. Dorsal stress fibers and transverse arcs rapidly responded within 15 min regardless of the strain magnitude to facilitate the subsequent changes in the orientation and elongation of the cytoplasm. The cyclic stretches induced the additional formation of perinuclear cap fibers and their increased number was almost maintained with a slight decline after 2-h-long stretch release. The slow formation and high stability of perinuclear cap fibers were linked to the slow reorientation kinetics and partial morphology recovery of nucleus in the presence or absence of cyclic stretches. The reorganization of stress fiber subtypes occurred in accordance with the reversible distribution of myosin II. These findings allowed us to propose a model for stretch-induced responses of the cytoplasm and nucleus in epithelial cells based on different mechanoadaptive properties of stress fiber subtypes.

scholarly journals Myosin II phosphorylation and the dynamics of stress fibers in serum-deprived and stimulated fibroblasts.

1992 ◽  
Vol 3 (9) ◽  
pp. 1037-1048 ◽  
Author(s):  
K A Giuliano ◽  
J Kolega ◽  
R L DeBiasio ◽  
D L Taylor
Keyword(s):  
Molecular Motors ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Myosin Ii ◽  
Stress Fiber ◽  
Stress Fibers ◽  
Serum Stimulation ◽  
Fiber Fragmentation ◽  
Distribution Of Stress ◽  
Massive Cell

The actin-based cytomatrix generates stress fibers containing a host of proteins including actin and myosin II and whose dynamics are easily observable in living cells. We developed a dual-radioisotope-based assay of myosin II phosphorylation and applied it to serum-deprived fibroblasts treated with agents that modified the dynamic distribution of stress fibers and/or altered the phosphorylation state of myosin II. Serum-stimulation induced an immediate and sustained increase in the level of myosin II heavy chain (MHC) and 20-kDa light chain (LC20) phosphorylation over the same time course that it caused stress fiber contraction. Cytochalasin D, shown to cause stress fiber fragmentation and contraction, had little effect on myosin II phosphorylation. Okadaic acid, a protein phosphatase inhibitor, induced a delayed but massive cell shortening preceded by a large increase in MHC and LC20 phosphorylation. Staurosporine, a kinase inhibitor known to effect dissolution but not contraction of stress fibers, immediately caused an increase in MHC and LC20 phosphorylation followed within minutes by the dephosphorylation of LC20 to a level below that of untreated cells. We therefore propose that the contractility of the actin-based cytomatrix is regulated by both modulating the activity of molecular motors such as myosin II and by altering the gel structure in such a manner as to either resist or yield to the tension applied by the motors.

Contractility Affects Stress Fiber Remodeling and Reorientation of the Endothelial Cells in Response to Mechanical Stretching

1999 ◽  
Author(s):  
James H.-C. Wang ◽  
Frank C.-P. Yin
Keyword(s):  
Cell Shape ◽  
Stress Fiber ◽  
Stress Fibers ◽  
Dependent Manner ◽  
Mechanical Stimuli ◽  
Cyclic Stretching ◽  
Cell Reorientation ◽  
Mlc Phosphorylation ◽  
Mechanical Stretching ◽  
Dose Dependent

Abstract Actin cytoskeletal stress fibers are thought to be the major cellular constituents responsible for cell shape and locomotion. As such, stress fiber remodeling likely plays a major role in the cell reorientation responses to mechanical stimuli (Iba and Sumpio, 1991). The assembly and dis-assembly of stress fibers in non-muscle cells are mediated by contractility via the interaction of actin and myosin (Chrzanowska-Wodnicka and Burridge, 1996). Reactive oxygen species (ROS) also play an important role in organization of stress fibers (Hinshaw et al., 1991). Since cyclic stretching can enhance production of certain ROS, including H2O2 (Howard et al., 1997) and H2O2 stimulates, in a time- and dose-dependent manner, myosin light chain (MLC) phosphorylation (Zhao and Davis, 1998), stress fiber remodeling and cell reorientation in response to cyclic stretching should be affected by changes in contractility — including changes in ROS. The roles of these factors have not been carefully examined.

scholarly journals The Mechanical Contribution of Vimentin to Cellular Stress Generation

2018 ◽  
Vol 140 (6) ◽  
Author(s):  
Inge A. E. W. van Loosdregt ◽  
Giulia Weissenberger ◽  
Marc P. F. H. L. van Maris ◽  
Cees W. J. Oomens ◽  
Sandra Loerakker ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Cellular Stress ◽  
Stress Fiber ◽  
Stress Generation ◽  
Stress Fibers ◽  
Adherent Cells ◽  
Wild Type ◽  
Contractile Stress ◽  
Fiber Organization ◽  
Fiber Contraction

Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between the stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study. We hypothesized that net stress generation comprises the stress fiber contraction combined with the vimentin resistance. We expected an increased net stress in vimentin knockout (VimKO) mouse embryonic fibroblasts (MEFs) compared to their wild-type (vimentin wild-type (VimWT)) counterparts, due to the decreased resistance against stress fiber contractility. To test this, the net stress generation by VimKO and VimWT MEFs was determined using the thin film method combined with sample-specific finite element modeling. Additionally, focal adhesion and stress fiber organization were examined via immunofluorescent staining. Net stress generation of VimKO MEFs was three-fold higher compared to VimWT MEFs. No differences in focal adhesion size or stress fiber organization and orientation were found between the two cell types. This suggests that the increased net stress generation in VimKO MEFs was caused by the absence of the resistance that vimentin provides against stress fiber contraction. Taken together, these data suggest that vimentin resists the stress fiber contractility, as hypothesized, thus indicating the importance of vimentin in regulating cellular stress generation by adherent cells.

scholarly journals Calcium-Sensing Receptor Stimulation in Cultured Glomerular Podocytes Induces TRPC6-Dependent Calcium Entry and RhoA Activation

2017 ◽  
Vol 43 (5) ◽  
pp. 1777-1789 ◽  
Author(s):  
Lei Zhang ◽  
Tianrong Ji ◽  
Qin Wang ◽  
Kexin Meng ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Protective Action ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Stress Fibers ◽  
Dependent Manner ◽  
Calcium Sensing Receptor ◽  
Rhoa Activity ◽  
Rhoa Activation ◽  
Calcium Sensing

Background/Aims: Recent studies provided compelling evidence that stimulation of the calcium sensing receptor (CaSR) exerts direct renoprotective action at the glomerular podocyte level. This protective action may be attributed to the RhoA-dependent stabilization of the actin cytoskeleton. However, the underlying mechanisms remain unclear. Methods: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure canonical transient receptor potential 6 (TRPC6) protein expression and RhoA activity. Stress fibers were detected by FITC-phalloidin. Results: Activating CaSR with a high extracellular Ca2+ concentration ([Ca2+]o) or R-568 (a type II CaSR agonist) induces an increase in the [Ca2+]i in a dose-dependent manner. This increase in [Ca2+]i is phospholipase C (PLC)-dependent and is smaller in the absence of extracellular Ca2+ than in the presence of 0.5 mM [Ca2+]o. The CaSR activation-induced [Ca2+]i increase is attenuated by the pharmacological blockage of TRPC6 channels or siRNA targeting TRPC6. These data suggest that TRPC6 is involved in CaSR activation-induced Ca2+ influx. Consistent with a previous study, CaSR stimulation results in an increase in RhoA activity. However, the knockdown of TRPC6 significantly abolished the RhoA activity increase induced by CaSR stimulation, suggesting that TRPC6-dependent Ca2+ entry is required for RhoA activation. The activated RhoA is involved in the formation of stress fibers and focal adhesions in response to CaSR stimulation because siRNA targeting RhoA attenuated the increase in the stress fiber mediated by CaSR stimulation. Moreover, this effect of CaSR activation on the formation of stress fibers is also abolished by the knockdown of TRPC6. Conclusion: TRPC6 is involved in the regulation of stress fiber formation and focal adhesions via the RhoA pathway in response to CaSR activation. This may explain the direct protective action of CaSR agonists.

scholarly journals Delayed stress fiber formation mediates pulmonary myofibroblast differentiation in response to TGF-β

2011 ◽  
Vol 301 (5) ◽  
pp. L656-L666 ◽  
Author(s):  
Nathan Sandbo ◽  
Andrew Lau ◽  
Jacob Kach ◽  
Caitlyn Ngam ◽  
Douglas Yau ◽  
...  
Keyword(s):  
Rho Kinase ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Stress Fibers ◽  
Nuclear Accumulation ◽  
Myofibroblast Differentiation ◽  
Latrunculin B ◽  
Stress Fiber Formation ◽  
Actin Expression ◽  
Actin Stress Fibers

Myofibroblast differentiation induced by transforming growth factor-β (TGF-β) and characterized by de novo expression of smooth muscle (SM)-specific proteins is a key process in wound healing and in the pathogenesis of fibrosis. We have previously shown that TGF-β-induced expression and activation of serum response factor (SRF) is required for this process. In this study, we examined the signaling mechanism for SRF activation by TGF-β as it relates to pulmonary myofibroblast differentiation. TGF-β stimulated a profound, but delayed (18–24 h), activation of Rho kinase and formation of actin stress fibers, which paralleled SM α-actin expression. The translational inhibitor cycloheximide blocked these processes without affecting Smad-dependent gene transcription. Inhibition of Rho kinase by Y-27632 or depolymerization of actin by latrunculin B resulted in inhibition TGF-β-induced SRF activation and SM α-actin expression, having no effect on Smad signaling. Conversely, stabilization of actin stress fibers by jasplakinolide was sufficient to drive these processes in the absence of TGF-β. TGF-β promoted a delayed nuclear accumulation of the SRF coactivator megakaryoblastic leukemia-1 (MKL1)/myocardin-related transcription factor-A, which was inhibited by latrunculin B. Furthermore, TGF-β also induced MKL1 expression, which was inhibited by latrunculin B, by SRF inhibitor CCG-1423, or by SRF knockdown. Together, these data suggest a triphasic model for myofibroblast differentiation in response to TGF-β that involves 1) initial Smad-dependent expression of intermediate signaling molecules driving Rho activation and stress fiber formation, 2) nuclear accumulation of MKL1 and activation of SRF as a result of actin polymerization, and 3) SRF-dependent expression of MKL1, driving further myofibroblast differentiation.

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