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

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.

Author(s):  
Zhensong Wei ◽  
Vikram S. Deshpande ◽  
Robert M. McMeeking ◽  
Anthony G. Evans

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.


2000 ◽  
Author(s):  
Hiroshi Yamada ◽  
Tohru Takemasa ◽  
Takami Yamaguchi

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.


2012 ◽  
Vol 302 (10) ◽  
pp. C1469-C1478 ◽  
Author(s):  
Kazuaki Nagayama ◽  
Yuki Kimura ◽  
Narutaka Makino ◽  
Takeo Matsumoto

Actin stress fibers (SFs) of cells cultured on cyclically stretched substrate tend to reorient in the direction in which a normal strain of substrate becomes zero. However, little is known about the mechanism of this reorientation. Here we investigated the effects of cyclic stretch waveform on SF reorientation in osteoblastic cells. Cells adhering to silicone membranes were subjected to cyclic uniaxial stretch, having one of the following waveforms with an amplitude of 8% for 24 h: triangular, trapezoid, bottom hold, or peak hold. SF reorientation of these cells was then analyzed. No preferential orientation was observed for the triangular and the peak-hold waveforms, whereas SFs aligned mostly in the direction with zero normal strain (∼55°) with other waveforms, especially the trapezoid waveform, which had a hold time both at loaded and unloaded states. Viscoelastic properties of SFs were estimated in a quasi-in situ stress relaxation test using intact and SF-disrupted cells that maintained their shape on the substrate. The dynamics of tension FSFsacting on SFs during cyclic stretching were simulated using these properties. The simulation demonstrated that FSFsdecreased gradually during cyclic stretching and exhibited a compressive value (FSFs< 0). The magnitude and duration time of the compressive forces were relatively larger in the group with a trapezoid waveform. The frequency of SF orientation had a significant negative correlation with the applied compressive forces integrated with time in a strain cycle, and the integrated value was largest with the trapezoid waveform. These results may indicate that the applied compressive forces on SFs have a significant effect on the stretch-induced reorientation of SFs, and that SFs realigned to avoid their compression. Stress relaxation of SFs might be facilitated during the holding period in the trapezoid waveform, and depolymerization and reorientation of SFs were significantly accelerated by their viscoelastic compression.


1989 ◽  
Vol 109 (1) ◽  
pp. 331-339 ◽  
Author(s):  
V P Shirinsky ◽  
A S Antonov ◽  
K G Birukov ◽  
A V Sobolevsky ◽  
Y A Romanov ◽  
...  

Human umbilical vein endothelial cells (EC) were grown on elastic silicone membranes subjected to cyclic stretch, simulating arterial wall motion. Stretching conditions (20% amplitude, 52 cycle/min) stimulated stress fiber formation and their orientation transversely to the strain direction. Cell bodies aligned along the same axis after the actin cytoskeleton. EC orientation response was inhibited by the adenylate cyclase activator, forskolin (10(-5) M), which caused stress fiber disassembly and the redistribution of F-actin to the cortical cytoplasm. Preoriented EC depleted of stress fibers by forskolin treatment retained their aligned state. Thus, stress fibers are essential for the process of EC orientation induced by repeated strain, but not for the maintenance of EC orientation. The monolayer formed by EC grown to confluence in conditions of intermittent strain consisted of uniform elongated cells and was resistant to deformation. In contrast, the monolayer assembled in stationary conditions was less compliant and exposed local denudations on initiation of stretching. When stretched in the presence of 10(-5) M forskolin it rapidly (3-4 h) reestablished integrity but gained a heterogeneous appearance since denuded areas were covered by giant cells. The protective effect of forskolin was because of the stimulation of EC spreading. This feature of forskolin was demonstrated while studying its action on EC spreading and repair of a scratched EC monolayer in conventional culture. Thus mechanical deformation and adenylate cyclase activity may be important factors in the control of endothelium morphology in human arteries.


2012 ◽  
Vol 23 (10) ◽  
pp. 1846-1859 ◽  
Author(s):  
Laura M. Hoffman ◽  
Christopher C. Jensen ◽  
Aashi Chaturvedi ◽  
Masaaki Yoshigi ◽  
Mary C. Beckerle

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.


2019 ◽  
Author(s):  
Aritra Chatterjee ◽  
Paturu Kondaiah ◽  
Namrata Gundiah

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.


2004 ◽  
Vol 126 (5) ◽  
pp. 545-551 ◽  
Author(s):  
Jeremiah J. Wille ◽  
Christina M. Ambrosi ◽  
Frank C-P Yin

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.


Author(s):  
Yunfeng Yang ◽  
Kazuaki Nagayama ◽  
Takeo Matsumoto

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].


1986 ◽  
Vol 103 (1) ◽  
pp. 63-70 ◽  
Author(s):  
G E White ◽  
K Fujiwara

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.


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