Strain waveform dependence of stress fiber reorientation in cyclically stretched osteoblastic cells: effects of viscoelastic compression of stress fibers

2012 ◽  
Vol 302 (10) ◽  
pp. C1469-C1478 ◽  
Author(s):  
Kazuaki Nagayama ◽  
Yuki Kimura ◽  
Narutaka Makino ◽  
Takeo Matsumoto
Keyword(s):  
Stress Relaxation ◽  
Hold Time ◽  
Significant Negative Correlation ◽  
In Situ Stress ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Osteoblastic Cells ◽  
Normal Strain ◽  
Holding Period ◽  
Cyclic Stretching

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.

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.

Low Serum Levels of Fibroblast Growth Factor 2 in Gunn Rats: A Hyperbilirubinemia Animal Model of Schizophrenic Symptoms

2020 ◽  
Vol 19 (7) ◽  
pp. 503-508
Author(s):  
Maiko Hayashida ◽  
Sadayuki Hashioka ◽  
Kenji Hayashida ◽  
Shoko Miura ◽  
Keiko Tsuchie ◽  
...  
Keyword(s):  
Animal Model ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Wistar Rats ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Strain ◽  
Fibroblast Growth ◽  
Gunn Rats

Background: Fibroblast growth factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and pro-differentiation of neurons. Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms. Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of unconjugated bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 at serum levels in all the rats studied. Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have anti-neuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which disbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles.

Mechanically Optimized Orientation of Intracellular Stress Fibers Under Cyclic Stretch

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.

Differential effects of static and cyclic stretching during elastase digestion on the mechanical properties of extracellular matrices

2007 ◽  
Vol 103 (3) ◽  
pp. 803-811 ◽  
Author(s):  
Rajiv Jesudason ◽  
Lauren Black ◽  
Arnab Majumdar ◽  
Phillip Stone ◽  
Bela Suki
Keyword(s):  
Mechanical Properties ◽  
Enzyme Activity ◽  
Failure Stress ◽  
Cyclic Stretch ◽  
Mechanical Forces ◽  
Peak Strain ◽  
Static Stretch ◽  
Cyclic Stretching ◽  
Rate Dependent ◽  
Physiological Processes

Enzyme activity plays an essential role in many physiological processes and diseases such as pulmonary emphysema. While the lung is constantly exposed to cyclic stretching, the effects of stretch on the mechanical properties of the extracellular matrix (ECM) during digestion have not been determined. We measured the mechanical and failure properties of elastin-rich ECM sheets loaded with static or cyclic uniaxial stretch (40% peak strain) during elastase digestion. Quasistatic stress-strain measurements were taken during 30 min of digestion. The incremental stiffness of the sheets decreased exponentially with time during digestion. However, digestion in the presence of static stretch resulted in an accelerated stiffness decrease, with a time constant that was nearly 3× smaller (7.1 min) than during digestion alone (18.4 min). These results were supported by simulations that used a nonlinear spring network model. The reduction in stiffness was larger during static than cyclic stretch, and the latter also depended on the frequency. Stretching at 20 cycles/min decreased stiffness less than stretching at 5 cycles/min, suggesting a rate-dependent coupling between mechanical forces and enzyme activity. Furthermore, pure digestion reduced the failure stress of the sheets from 88 ± 21 kPa in control to 29 ± 15 kPa ( P < 0.05), while static and cyclic stretch resulted in a failure stress of 7 ± 5 kPa ( P < 0.05). We conclude that not only the presence but the dynamic nature of mechanical forces have a significant impact on enzyme activity, hence the deterioration of the functional properties of the ECM during exposure to enzymes.

Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers

2021 ◽  
Author(s):  
Wenjing Huang ◽  
Tsubasa S. Matsui ◽  
Takumi Saito ◽  
Masahiro Kuragano ◽  
Masayuki Takahashi ◽  
...  
Keyword(s):  
Cellular Response ◽  
Early Stage ◽  
Myosin Ii ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Chronic Activation ◽  
Selective Disassembly ◽  
Actin Stress Fibers

Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here we suggest that the mechanosensitive behavior of myosin II, a major cross-linker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.

Notch-Strengthening Phenomenon Under Creep-Fatigue Loading Conditions

1999 ◽  
Vol 122 (1) ◽  
pp. 15-21 ◽  
Author(s):  
N. Merah
Keyword(s):  
Experimental Data ◽  
Stress Relaxation ◽  
Notch Root ◽  
Hold Time ◽  
Local Stress ◽  
Frequency Effect ◽  
Strengthening Effect ◽  
Strain Accumulation ◽  
Element Analysis ◽  
Creep Fatigue

A study of the notch and frequency effects on fatigue life at high temperature is carried out using notched and unnotched plate specimens of SS 304 under stress-controlled testing conditions. Analysis of the σ-Nf results obtained at 600°C under fatigue and creep-fatigue conditions allowed the generalization of the σ-Nf-Kt relation proposed in an earlier study. Examinations of the experimental data with hold-time testing suggested that in these conditions, the frequency effect should be incorporated in the relationship. Results obtained from the modified relation are in agreement with the experimental data, within a factor of two. Finite element analysis was carried out to determine the state of stresses and strains at the notch root by simulating four creep-fatigue cycles. The computed results indicated that, under zero-to-tension cyclic loading with controlled nominal stress, the maximum local stress at the notch root relaxes; this results in a minimum local stress in compression, and as a consequence, the mean local stress is significantly reduced. The stress relaxation as well as the creep strain accumulation were found to occur only in the vicinity of the notch (within 0.75 mm). The numerical results concerning the local stress relaxation and the time-dependent strain accumulation are used to explain the notch-strengthening effect on life observed in the present study. [S0094-9930(00)00401-7]

scholarly journals Mechanical Stretch Kills Transformed Cancer Cells

2018 ◽  
Author(s):  
Ajay Tijore ◽  
Mingxi Yao ◽  
Yu-Hsiu Wang ◽  
Yasaman Nematbakhsh ◽  
Anushya Hariharan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Cyclic Stretch ◽  
Transformed Cells ◽  
Normal Cells ◽  
Calcium Dependent ◽  
Cyclic Stretching ◽  
Protease Activation ◽  
Different Tissues

AbstractTransformed cancer cells differ from normal cells in several important features like anchorage independence, Warburg effect and mechanosensing. Consequently, transformed cancer cells develop an anaplastic morphology and respond aberrantly to external mechanical forces. Consistent with altered mechano-responsiveness, here we show that transformed cancer cells from many different tissues have reduced growth and become apoptotic upon cyclic stretch as do normal cells after the transformation. When matrix rigidity sensing is restored in transformed cancer cells, they survive and grow faster on soft surface upon cyclic stretch like normal cells but undergo anoikis without stretch by activation of death associated protein kinase1 (DAPK1). In contrast, stretch-dependent apoptosis (mechanoptosis) of transformed cells is driven by stretch-mediated calcium influx and calcium-dependent calpain 2 protease activation on both collagen and fibronectin matrices. Further, mechanosensitive calcium channel, Piezo1 is needed for mechanoptosis. Thus, cyclic stretching of transformed cells from different tissues activates apoptosis, whereas similar stretching of normal cells stimulates growth.

Residual Stress Relaxation in a Tube Attachment Weld Inside a Pressure Vessel Forging During Post Weld Heat Treatment

2007 ◽  
Author(s):  
P. R. Hurrell ◽  
J. Davies ◽  
N. A. Leggatt ◽  
R. J. Dennis ◽  
R. H. Leggatt
Keyword(s):  
Heat Treatment ◽  
Residual Stress ◽  
Stress Relaxation ◽  
Pressure Vessel ◽  
Hold Time ◽  
Stress Relief ◽  
Post Weld Heat Treatment ◽  
Secondary Creep ◽  
Axial Tensile ◽  
Weld Heat

This paper presents analyses done to determine residual stress relief achieved by post weld heat treatment (PWHT) of tube attachment welds inside a thick SA508 steel pressure vessel forging. Finite element (FE) analyses were performed modelling the manufacturing operations in detail including welding, machining and PWHT. The analyses demonstrate that PWHT at 600°C for 8 hours is effective in reducing as-welded residual stress levels from tensile yield magnitude (+500MPa approx) to &lt;100MPa. The maximum residual stress was computed to be 90MPa sub-surface in a region of hydrostatic (tri-axial tensile) stress. Secondary creep was modelled using data from creep tests on SA508 steel uni-axial tensile specimens. Practically all of the stress relaxation is due to creep strain with minimal additional plastic strain. Most stress relief occurs during the first hour of soak, with diminishing benefit thereafter. Analysis results also indicate that PWHT effectiveness is more sensitive to soak temperature than hold time. These FE results are considered slightly pessimistic but are reasonably consistent with other analytical predictions. By comparison surface hole drilling stress measurements of &lt;50MPa (10% yield strength) were recorded from a representative welded test block. Analysis pessimism was attributed to ignoring both primary creep and relaxation during the slow warm up phase of the heat treatment cycle.

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