Cyclic stretch-induced stress fiber dynamics – Dependence on strain rate, Rho-kinase and MLCK

Reinforcement of actin stress fibers in response to mechanical stimulation depends on a posttranslational mechanism that requires the LIM protein zyxin. The C-terminal LIM region of zyxin directs the force-sensitive accumulation of zyxin on actin stress fibers. The N-terminal region of zyxin promotes actin reinforcement even when Rho kinase is inhibited. The mechanosensitive integrin effector p130Cas binds zyxin but is not required for mitogen-activated protein kinase–dependent zyxin phosphorylation or stress fiber remodeling in cells exposed to uniaxial cyclic stretch. α-Actinin and Ena/VASP proteins bind to the stress fiber reinforcement domain of zyxin. Mutation of their docking sites reveals that zyxin is required for recruitment of both groups of proteins to regions of stress fiber remodeling. Zyxin-null cells reconstituted with zyxin variants that lack either α-actinin or Ena/VASP-binding capacity display compromised response to mechanical stimulation. Our findings define a bipartite mechanism for stretch-induced actin remodeling that involves mechanosensitive targeting of zyxin to actin stress fibers and localized recruitment of actin regulatory machinery.

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Dependence of Cyclic Stretch-Induced Stress Fiber Reorientation on Stretch Waveform

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80778 ◽

2012 ◽

Author(s):

Abhishek Tondon ◽

Hui-Ju Hsu ◽

Roland Kaunas

Keyword(s):

Stress Fiber ◽

Cyclic Stretch ◽

Induced Stress ◽

Fiber Reorientation

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Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch

10.1101/622092 ◽

2019 ◽

Author(s):

Aritra Chatterjee ◽

Paturu Kondaiah ◽

Namrata Gundiah

Keyword(s):

Effective Elastic Modulus ◽

Stress Fiber ◽

Cyclic Stretch ◽

Stress Fibers ◽

Avoidance Reaction ◽

Cortical Actin ◽

Fiber Growth ◽

Induced Stress ◽

Reorientation Dynamics ◽

And Migration

AbstractStress fibers in the cytoskeleton are essential in maintaining cellular shape, and influence their adhesion and migration. Cyclic uniaxial stretching results in cellular reorientation orthogonal to the applied stretch direction via a strain avoidance reaction; the mechanistic cues in cellular mechanosensitivity to this response are currently underexplored. We show stretch induced stress fiber lengthening, their realignment and increased cortical actin in fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and alignment of stress fibers were accompanied with an increase in the effective elastic modulus of cells. Microtubules did not contribute to the measured stiffness or reorientation response but were essential to the nuclear reorientation. We modeled stress fiber growth and reorientation dynamics using a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the observed fibroblast morphology and increased cellular stiffness under uniaxial cyclic stretch. These studies are important in exploring the differences underlying mechanotransduction and cellular contractility under stretch.

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Stretch-Induced Stress Fiber Remodeling and the Activations of JNK and ERK Depend on Mechanical Strain Rate, but Not FAK

PLoS ONE ◽

10.1371/journal.pone.0012470 ◽

2010 ◽

Vol 5 (8) ◽

pp. e12470 ◽

Cited By ~ 108

Author(s):

Hui-Ju Hsu ◽

Chin-Fu Lee ◽

Andrea Locke ◽

Susan Q. Vanderzyl ◽

Roland Kaunas

Keyword(s):

Strain Rate ◽

Mechanical Strain ◽

Stress Fiber ◽

Induced Stress

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The Direction of Cyclic Stretch-Induced Stress Fiber Orientation Depends on Matrix Rigidity

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53501 ◽

2011 ◽

Author(s):

Abhishek Tondon ◽

Hui-Ju Hsu ◽

Roland Kaunas

Keyword(s):

Theoretical Model ◽

Fiber Orientation ◽

Stress Fiber ◽

Cyclic Stretch ◽

Matrix Rigidity ◽

Structural Element ◽

Cellular Processes ◽

Induced Stress ◽

Cellular Environment ◽

Collagen Hydrogels

Mechanical properties of the cellular environment such as elastic rigidity have been shown to play an important role in the regulation of important cellular processes such as proliferation, differentiation and apoptosis (1–3). Intracellular tension decreases with decreasing matrix rigidity (1). Actin stress fibers (SFs), the major structural element in cells bearing tension, are also less prevalent on soft vs. rigid matrices (4). We have developed a theoretical model of stretch-induced SFs that predicts SFs reorient perpendicular to the direction of cyclic stretch in order to maintain SF tension at a homeostatic level (5). A theoretical model developed by the Safran group (6) predicts that cells will also align perpendicular to cyclic stretch on soft substrates. To test these predictions, we subjected cells to cyclic uniaxial stretch on soft collagen hydrogels. Interestingly, the cells and their SFs aligned parallel to the direction of stretch without co-alignment of collagen fibrils, indicating the need for a new model to describe the effects of cyclic stretch on SF reorganization on soft matrices.

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Synergy between Rho signaling and matrix density in cyclic stretch-induced stress fiber organization

Acta Biomaterialia ◽

10.1016/j.actbio.2013.12.001 ◽

2014 ◽

Vol 10 (5) ◽

pp. 1876-1885 ◽

Cited By ~ 21

Author(s):

Jasper Foolen ◽

Marloes W.J.T. Janssen-van den Broek ◽

Frank P.T. Baaijens

Keyword(s):

Stress Fiber ◽

Cyclic Stretch ◽

Matrix Density ◽

Induced Stress ◽

Fiber Organization

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Dependence of cyclic stretch-induced stress fiber reorientation on stretch waveform

Journal of Biomechanics ◽

10.1016/j.jbiomech.2011.11.012 ◽

2012 ◽

Vol 45 (5) ◽

pp. 728-735 ◽

Cited By ~ 49

Author(s):

Abhishek Tondon ◽

Hui-Ju Hsu ◽

Roland Kaunas

Keyword(s):

Stress Fiber ◽

Cyclic Stretch ◽

Induced Stress ◽

Fiber Reorientation

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RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3

AJP Renal Physiology ◽

10.1152/ajprenal.00295.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. F1054-F1064 ◽

Cited By ~ 10

Author(s):

Xiaojing Yang ◽

Hai-Chang Huang ◽

Helen Yin ◽

Robert J. Alpern ◽

Patricia A. Preisig

Keyword(s):

Tyrosine Phosphorylation ◽

Focal Adhesion ◽

Apical Membrane ◽

Rho Kinase ◽

Stress Fiber ◽

Fiber Formation ◽

Adhesion Proteins ◽

Stress Fiber Formation ◽

Induced Stress ◽

Focal Adhesion Proteins

Exposure to an acid load increases apical membrane Na+/H+ antiporter (NHE3) activity, a process that involves exocytic trafficking of the transporter to the apical membrane. We have previously shown that an intact microfilament structure is required for this exocytic process (Yang X, Amemiya M, Peng Y, Moe OW, Preisig PA, Alpern RJ. Am J Physiol Cell Physiol 279: C410–C419, 2000). The present studies demonstrate that acid-induced stress fiber formation is required for stimulation of NHE3 activity. Formation of stress fibers is associated with acid-induced tyrosine phosphorylation and increases in protein abundance of two focal adhesion proteins, p125FAK and paxillin. The Rho kinase inhibitor Y27632 completely blocks acid-induced stress fiber formation and the increases in apical membrane NHE3 abundance and activity, but it has no effect on acid-induced tyrosine phosphorylation of p125FAK or paxillin. Herbimycin A completely blocks acid-induced tyrosine phosphorylation of p125FAK and paxillin but only partially blocks stress fiber formation and NHE3 activation. These studies demonstrate that Rho kinase mediates acid-induced stress fiber formation, which is required for NHE3 exocytosis, and increases in NHE3 activity. Acid-induced tyrosine phosphorylation of the focal adhesion proteins p125FAK and paxillin is not Rho kinase dependent. Thus these two acid-mediated effects are associated, yet independent processes.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00166.2011 ◽

2011 ◽

Vol 301 (5) ◽

pp. L656-L666 ◽

Cited By ~ 65

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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Mechanically Optimized Orientation of Intracellular Stress Fibers Under Cyclic Stretch

10.1115/imece2000-1419 ◽

2000 ◽

Author(s):

Hiroshi Yamada ◽

Tohru Takemasa ◽

Takami Yamaguchi

Keyword(s):

Endothelial Cell ◽

Continuum Mechanics ◽

Cellular Response ◽

Length Change ◽

Mechanical Stimulus ◽

Stress Fiber ◽

Cyclic Stretch ◽

Stress Fibers ◽

Biological Phenomenon ◽

The Continuum

Abstract To elucidate the orientation of stress fibers in a cultured endothelial cell under cyclic stretch, we hypothesized that a stress fiber aligns so as to minimize the summation of its length change under cyclic stretch, and that there is a limit in the sensitivity of cellular response to the mechanical stimulus. Results from numerical simulations based on the continuum mechanics describe the experimental observations under uniaxial stretch well. They give us an insight to the biological phenomenon of the orientation in stress fibers under biaxial stretch from the viewpoint of mechanical engineering.

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