scholarly journals Emergence of Mechano-Sensitive Contraction Autoregulation in Cardiomyocytes

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 503
Author(s):  
Leighton Izu ◽  
Rafael Shimkunas ◽  
Zhong Jian ◽  
Bence Hegyi ◽  
Mohammad Kazemi-Lari ◽  
...  
Keyword(s):  
Mechanical Load ◽  
Mechanical Strain ◽  
General System ◽  
Feedback Mechanism ◽  
Contraction Force ◽  
Initial State ◽  
Contraction Amplitude ◽  
Chamber Volume ◽  
Model Predictions ◽  
Stress Dependent

The heart has two intrinsic mechanisms to enhance contractile strength that compensate for increased mechanical load to help maintain cardiac output. When vascular resistance increases the ventricular chamber initially expands causing an immediate length-dependent increase of contraction force via the Frank-Starling mechanism. Additionally, the stress-dependent Anrep effect slowly increases contraction force that results in the recovery of the chamber volume towards its initial state. The Anrep effect poses a paradox: how can the cardiomyocyte maintain higher contractility even after the cell length has recovered its initial length? Here we propose a surface mechanosensor model that enables the cardiomyocyte to sense different mechanical stresses at the same mechanical strain. The cell-surface mechanosensor is coupled to a mechano-chemo-transduction feedback mechanism involving three elements: surface mechanosensor strain, intracellular Ca2+ transient, and cell strain. We show that in this simple yet general system, contractility autoregulation naturally emerges, enabling the cardiomyocyte to maintain contraction amplitude despite changes in a range of afterloads. These nontrivial model predictions have been experimentally confirmed. Hence, this model provides a new conceptual framework for understanding the contractility autoregulation in cardiomyocytes, which contributes to the heart’s intrinsic adaptivity to mechanical load changes in health and diseases.

scholarly journals E11/gp38 Selective Expression in Osteocytes: Regulation by Mechanical Strain and Role in Dendrite Elongation

2006 ◽  
Vol 26 (12) ◽  
pp. 4539-4552 ◽  
Author(s):  
Keqin Zhang ◽  
Cielo Barragan-Adjemian ◽  
Ling Ye ◽  
Shiva Kotha ◽  
Mark Dallas ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cell Lines ◽  
Mechanical Load ◽  
Mechanical Strain ◽  
Three Dimensional ◽  
Cell Communication ◽  
Bone Surface ◽  
Cellular Processes ◽  
Primary Osteoblasts

ABSTRACT Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells. Bone extracts contain large amounts of E11, but immunostaining only shows its presence in early osteocytes compared to more deeply embedded cells, suggesting epitope masking by mineral. Freshly isolated primary osteoblasts are negative for E11 expression but begin to express this protein in culture, and expression increases with time, suggesting differentiation into the osteocyte phenotype. Osteoblast-like cell lines 2T3 and Oct-1 also show increased expression of E11 with differentiation and mineralization. E11 is highly expressed in MLO-Y4 osteocyte-like cells compared to osteoblast cell lines and primary osteoblasts. Differentiated, mineralized 2T3 cells and MLO-Y4 cells subjected to fluid flow shear stress show an increase in mRNA for E11. MLO-Y4 cells show an increase in dendricity and elongation of dendrites in response to shear stress that is blocked by small interfering RNA specific to E11. In vivo, E11 expression is also increased by a mechanical load, not only in osteocytes near the bone surface but also in osteocytes more deeply embedded in bone. Maximal expression is observed not in regions of maximal strain but in a region of potential bone remodeling, suggesting that dendrite elongation may be occurring during this process. These data suggest that osteocytes may be able to extend their cellular processes after embedment in mineralized matrix and have implications for osteocytic modification of their microenvironment.

Selected Contribution: Regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells

2000 ◽  
Vol 89 (6) ◽  
pp. 2498-2507 ◽  
Author(s):  
M. A. Peake ◽  
L. M. Cooling ◽  
J. L. Magnay ◽  
P. B. M. Thomas ◽  
A. J. El Haj
Keyword(s):  
Bone Cells ◽  
Mechanical Load ◽  
Mechanical Strain ◽  
Collagen Type I ◽  
Bone Cell ◽  
Type I ◽  
Regulatory Pathways ◽  
Four Point Bending ◽  
Load Response ◽  
Factor C

The regulatory pathways involved in the rapid response of the AP-1 transcription factor, c- fos, to mechanical load in human primary osteoblast-like (HOB) cells and the human MG-63 bone cell line were investigated using a four-point bending model. HOB and MG-63 cells showed upregulation of c- fos expression on fibronectin and collagen type I substrates; however, MG-63 cells did not respond on laminin YIGSR substrates. Addition of cytochalasin D and Arg-Gly-Asp peptides during loading did not inhibit the response, whereas addition of β1-integrin antibodies inhibited the load response. The role of Ca2+ signaling has been demonstrated by blocking upregulation with addition of 2 mM EGTA, which chelates extracellular Ca2+, and gadolinium (10 μM), which inhibits stretch-activated channels. Addition of the Ca2+ ionophore A-23187 induced upregulation without loading; however, addition of nifedipine (10 μM), the L-type channel blocker, failed to prevent the load response. Inhibitors of downstream pathways indicated the involvement of protein kinase C. Our results demonstrate a key involvement of Ca2+ signaling pathways and integrin binding in the c- fos response to mechanical strain.

scholarly journals Static and dynamic effective stress coefficient of chalk

Geophysics ◽  
2012 ◽  
Vol 77 (2) ◽  
pp. L1-L11 ◽  
Author(s):  
M. Monzurul Alam ◽  
Ida Lykke Fabricius ◽  
Helle Foged Christensen
Keyword(s):  
Pore Pressure ◽  
Effective Stress ◽  
Mechanical Strain ◽  
Mechanical Tests ◽  
Differential Stress ◽  
Stress Regime ◽  
Hydrocarbon Reservoir ◽  
Stress Coefficient ◽  
The Difference ◽  
Stress Dependent

Deformation of a hydrocarbon reservoir can ideally be used to estimate the effective stress acting on it. The effective stress in the subsurface is the difference between the stress due to the weight of the sediment and a fraction (effective stress coefficient) of the pore pressure. The effective stress coefficient is thus relevant for studying reservoir deformation and for evaluating 4D seismic for the correct pore pressure prediction. The static effective stress coefficient [Formula: see text] is estimated from mechanical tests and is highly relevant for effective stress prediction because it is directly related to mechanical strain in the elastic stress regime. The corresponding dynamic effective stress coefficient [Formula: see text] is easy to estimate from density and velocity of acoustic (elastic) waves. We studied [Formula: see text] and [Formula: see text] of chalk from the reservoir zone of the Valhall field, North Sea, and found that [Formula: see text] and [Formula: see text] vary with differential stress (overburden stress-pore pressure). For Valhall reservoir chalk with 40% porosity, [Formula: see text] ranges between 0.98 and 0.85 and decreases by 10% if the differential stress is increased by 25 MPa. In contrast, for chalk with 15% porosity from the same reservoir, [Formula: see text] ranges between 0.85 and 0.70 and decreases by 5% due to a similar increase in differential stress. Our data indicate that [Formula: see text] measured from sonic velocity data falls in the same range as for [Formula: see text], and that [Formula: see text] is always below unity. Stress-dependent behavior of [Formula: see text] is similar (decrease with increasing differential stress) to that of [Formula: see text] during elastic deformation caused by pore pressure buildup, for example, during waterflooding. By contrast, during the increase in differential stress, as in the case of pore pressure depletion due to production, [Formula: see text] increases with stress while [Formula: see text] decreases.

Continuum Damage Model for Biodegradable Magnesium Alloy Stent

2010 ◽  
Vol 138 ◽  
pp. 85-91 ◽  
Author(s):  
Dario Gastaldi ◽  
Valentina Sassi ◽  
Lorenza Petrini ◽  
Maurizio Vedani ◽  
Stefano P. Trasatti ◽  
...  
Keyword(s):  
Damage Evolution ◽  
Mechanical Load ◽  
Corrosion Damage ◽  
Analytical Models ◽  
Material Strength ◽  
Uniform Corrosion ◽  
Continuum Damage ◽  
Evolution Law ◽  
Biodegradable Stents ◽  
Stress Dependent

The main drawback of conventional stenting procedure is the high risk of restenosis. The idea of a stent that "disappears" after having fulfilled its mission is very intriguing and fascinating. The stent mass should diminishing in time to allow the gradual transmission of the mechanical load to the surrounding tissues. Magnesium and its alloys seem to be among the most appealing materials to design biodegradable stents. The objective of this work is to develop, in a finite element (FE) framework, a model of magnesium degradation able to predict the corrosion rate and thus providing a valuable tool to design biodegradable stents. Continuum damage approach is suitable for modelling different damage mechanisms, including several types of corrosion. Corrosion is modelled by a scalar damage field which accounts for the material strength loss due to geometrical discontinuities. As damage progresses, the material stiffness decreases. Corrosion damage results as the superposition of stress corrosion process and uniform corrosion. The former describes the stress-mediated localization of the corrosion attack through a stress-dependent evolution law similar to the one used in analytical models, while the latter affects the free surface of the material exposed to an aggressive environment. The effects of both phenomena described are modelled through a linear composition of the two specific damage evolution laws. The model, developed in a FE framework, manages the mesh dependency, typical of strain-softening behaviour, including the FE characteristic length in the damage evolution law definition. The developed model is able to reproduce the behaviour of different magnesium alloys subjected to static and slow-strain-rate corrosion tests. Moreover, 3D stenting procedures accounting for the interaction with the arterial vessel are simulated.

scholarly journals Actinometric measurements of NO<sub>2</sub> photolysis frequencies in the atmosphere simulation chamber SAPHIR

2005 ◽  
Vol 5 (2) ◽  
pp. 493-503 ◽  
Author(s):  
B. Bohn ◽  
F. Rohrer ◽  
T. Brauers ◽  
A. Wahner
Keyword(s):  
Calibration Factor ◽  
Absolute Calibration ◽  
Chamber Volume ◽  
Photolysis Frequencies ◽  
Model Predictions ◽  
External Conditions ◽  
Atmosphere Simulation Chamber ◽  
Simulation Chamber ◽  
Model Approach

Abstract. The simulation chamber SAPHIR at Forschungszentrum Jülich has UV permeable teflon walls facilitating atmospheric photochemistry studies under the influence of natural sunlight. Because the internal radiation field is strongly affected by construction elements, we use external, radiometric measurements of spectral actinic flux and a model to calculate mean photolysis frequencies for the chamber volume Bohn04B. In this work we determine NO2 photolysis frequencies j(NO2) within SAPHIR using chemical actinometry by injecting NO2 and observing the chemical composition during illumination under various external conditions. In addition to a photo-stationary approach, a time-dependent method was developed to analyse the data. These measurements had two purposes. Firstly, to check the model predictions with respect to diurnal and seasonal variations in the presence of direct sunlight and secondly to obtain an absolute calibration factor for the combined radiometry-model approach. We obtain a linear correlation between calculated and actinometric j(NO2). A calibration factor of 1.34±0.10 is determined, independent of conditions in good approximation. This factor is in line with expectations and can be rationalised by internal reflections within the chamber. Taking into account the uncertainty of the actinometric j(NO2), an accuracy of 13% is estimated for the determination of j(NO2) in SAPHIR. In separate dark experiments a rate constant of (1.93±0.12)x10-14 cm3 s-1 was determined for the NO+O3 reaction at 298K using analytical and numerical methods of data analysis.

scholarly journals Design and Validation of Equiaxial Mechanical Strain Platform, EQUicycler, for 3D Tissue Engineered Constructs

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Mostafa Elsaadany ◽  
Matthew Harris ◽  
Eda Yildirim-Ayan
Keyword(s):  
Cell Lines ◽  
Mechanical Loading ◽  
Mechanical Load ◽  
Mechanical Strain ◽  
Three Dimensional ◽  
Cost Effective ◽  
Tissue Constructs ◽  
Tissue Systems

It is crucial to replicate the micromechanical milieu of native tissues to achieve efficacious tissue engineering and regenerative therapy. In this study, we introduced an innovative loading platform, EQUicycler, that utilizes a simple, yet effective, and well-controlled mechanism to apply physiologically relevant homogenous mechanical equiaxial strain on three-dimensional cell-embedded tissue scaffolds. The design of EQUicycler ensured elimination of gripping effects through the use of biologically compatible silicone posts for direct transfer of the mechanical load to the scaffolds. Finite Element Modeling (FEM) was created to understand and to quantify how much applied global strain was transferred from the loading mechanism to the tissue constructs. In vitro studies were conducted on various cell lines associated with tissues exposed to equiaxial mechanical loading in their native environment. In vitro results demonstrated that EQUicycler was effective in maintaining and promoting the viability of different musculoskeletal cell lines and upregulating early differentiation of osteoprogenitor cells. By utilizing EQUicycler, collagen fibers of the constructs were actively remodeled. Residing cells within the collagen construct elongated and aligned with strain direction upon mechanical loading. EQUicycler can provide an efficient and cost-effective tool to conduct mechanistic studies for tissue engineered constructs designed for tissue systems under mechanical loading in vivo.

scholarly journals Cartilage Strain Distributions Are Different Under the Same Load in the Central and Peripheral Tibial Plateau Regions

2015 ◽  
Vol 137 (12) ◽  
Author(s):  
Paul Briant ◽  
Scott Bevill ◽  
Thomas Andriacchi
Keyword(s):  
Articular Cartilage ◽  
Applied Load ◽  
Tibial Plateau ◽  
Mechanical Load ◽  
Cruciate Ligament ◽  
Mechanical Strain ◽  
Collagen Network ◽  
Maximum Shear Strain ◽  
Knee Oa ◽  
Peripheral Regions

There is increasing evidence that the regional spatial variations in the biological and mechanical properties of articular cartilage are an important consideration in the pathogenesis of knee osteoarthritis (OA) following kinematic changes at the knee due to joint destabilizing events (such as an anterior cruciate ligament (ACL) injury). Thus, given the sensitivity of chondrocytes to the mechanical environment, understanding the internal mechanical strains in knee articular cartilage under macroscopic loads is an important element in understanding knee OA. The purpose of this study was to test the hypothesis that cartilage from the central and peripheral regions of the tibial plateau has different internal strain distributions under the same applied load. The internal matrix strain distribution for each specimen was measured on osteochondral blocks from the tibial plateau of mature ovine stifle joints. Each specimen was loaded cyclically for 20 min, after which the specimen was cryofixed in its deformed position and freeze fractured. The internal matrix was viewed in a scanning electron microscope (SEM) and internal strains were measured by quantifying the deformation of the collagen fiber network. The peak surface tensile strain, maximum principal strain, and maximum shear strain were compared between the regions. The results demonstrated significantly different internal mechanical strain distributions between the central and peripheral regions of tibial plateau articular cartilage under both the same applied load and same applied nominal strain. These differences in the above strain measures were due to differences in the deformation patterns of the collagen network between the central and peripheral regions. Taken together with previous studies demonstrating differences in the biochemical response of chondrocytes from the central and peripheral regions of the tibial plateau to mechanical load, the differences in collagen network deformation observed in this study help to provide a fundamental basis for understanding the association between altered knee joint kinematics and premature knee OA.

Wiener and Luhmann on feedback: from complexity to sustainability

Kybernetes ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 386-399 ◽  
Author(s):  
Vladislav Valentinov
Keyword(s):  
General System ◽  
Feedback Mechanism ◽  
General Systems Theory ◽  
Theoretic Analysis ◽  
Content Type ◽  
System Environment ◽  
Controlled Systems ◽  
General Systems ◽  
The Cost

Purpose The rise of the general systems theory in the twentieth century would not have been possible without the concept of feedback. Of special interest to the present paper is Niklas Luhmann’s reconstruction and critique of Wiener’s cybernetic approach to the feedback concept. Luhmann has suggested that the operation of the feedback-controlled systems potentially poses problems of sustainability. The purpose of this paper is to explore this suggestion in more detail. Design/methodology/approach The reconstruction of the arguments of Luhmann and Wiener shows that both scholars approached the feedback concept from the “system-environment” perspective. Luhmann takes system-environment relations to be inherently precarious. Wiener underscores the importance of the sensitivity of the feedback-controlled systems to their environment. Findings Drawing on Norbert Wiener’s and Niklas Luhmann’s ideas, the paper shows that every specification of the feedback mechanism implies the drawing of the moral boundary that demarcates those parts of the environment to which the relevant system is sensitive from those to which it is not. A likely outcome of this boundary drawing is the maintenance of intra-systemic complexity at the cost of the deteriorating sustainability of the system in its environment. Originality/value Until today, the general system theory has sought to explain organized complexity and rightly underscored the role of feedback in maintaining it, thereby inadvertently creating the chasm between the complexity and sustainability dimensions of human civilization. The present paper pleads for reorienting of the systems-theoretic analysis of the feedback concept toward closing this chasm.

scholarly journals Ventilation-Like Mechanical Strain Modulates the Inflammatory Response of BEAS2B Epithelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Sashko G. Spassov ◽  
Christoph Kessler ◽  
Rebecca Jost ◽  
Stefan Schumann
Keyword(s):  
Mechanical Ventilation ◽  
Epithelial Cells ◽  
Mechanical Load ◽  
Mechanical Strain ◽  
Cyclic Strain ◽  
Mitochondrial Activity ◽  
Proinflammatory Response ◽  
Strain Profile ◽  
Nf Kappab ◽  
Temporal Profiles

Protective mechanical ventilation is aimed at preventing ventilator-induced lung injury while ensuring sufficient gas exchange. A new approach focuses on the temporal profile of the mechanical ventilation. We hypothesized that the temporal mechanical strain profile modulates inflammatory signalling. We applied cyclic strain with various temporal profiles to human bronchial epithelial cells (BEAS2B) and assessed proinflammatory response. The cells were subjected to sinusoidal, rectangular, or triangular strain profile and rectangular strain profile with prestrain set to 0, 25, 50, or 75% of the maximum stain, static strain, and strain resembling a mechanical ventilation-like profile with or without flow-controlled expiration. The BEAS2B response to mechanical load included altered mitochondrial activity, increased superoxide radical levels, NF-kappaB translocation, and release of interleukin-8. The response to strain was substantially modulated by the dynamics of the stimulation pattern. The rate of dynamic changes of the strain profile correlates with the degree of mechanical stress-induced cell response.

scholarly journals Actinometric measurements of NO<sub>2</sub> photolysis frequencies in the atmosphere simulation chamber SAPHIR

2004 ◽  
Vol 4 (6) ◽  
pp. 8141-8170
Author(s):  
B. Bohn ◽  
F. Rohrer ◽  
T. Brauers ◽  
A. Wahner
Keyword(s):  
Calibration Factor ◽  
Absolute Calibration ◽  
Chamber Volume ◽  
Photolysis Frequencies ◽  
Model Predictions ◽  
External Conditions ◽  
Atmosphere Simulation Chamber ◽  
Simulation Chamber ◽  
Model Approach

Abstract. The simulation chamber SAPHIR at Forschungszentrum Jülich has UV permeable teflon walls facilitating atmospheric photochemistry studies under the influence of natural sunlight. Because the internal radiation field is strongly affected by construction elements, we use external, radiometric measurements of spectral actinic flux and a model to calculate mean photolysis frequencies for the chamber volume (Bohn and Zilken, 2004). In this work we determine NO2 photolysis frequencies j(NO2) within SAPHIR using chemical actinometry by injecting NO2 and observing the chemical composition during illumination under various external conditions. In addition to a photo-stationary approach, a time-dependent method was developed to analyse the data. These measurements had two purposes. Firstly, to check the model predictions with respect to diurnal and seasonal variations in the presence of direct sunlight and secondly to obtain an absolute calibration factor for the combined radiometry-model approach. We obtain a linear correlation between calculated and actinometric j(NO2). A calibration factor of 1.34±0.10 is determined, independent of conditions in good approximation. This factor is in line with expectations and can be rationalised by internal reflections within the chamber. Taking into account the uncertainty of the actinometric j(NO2), an accuracy of 13% is estimated for the determination of j(NO2) in SAPHIR. In separate dark experiments a rate constant of (1.93±0.12)×10−14 cm3 s−1 was determined for the NO+O3 reaction at 298 K using analytical and numerical methods of data analysis.

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