Computational Analyses of Mechanically Induced Collagen Fiber Remodeling in the Aortic Heart Valve

2003 ◽  
Vol 125 (4) ◽  
pp. 549-557 ◽  
Author(s):  
Niels J. B. Driessen ◽  
Ralf A. Boerboom ◽  
Jacques M. Huyghe ◽  
Carlijn V. C. Bouten ◽  
Frank P. T. Baaijens

To optimize the mechanical properties and integrity of tissue-engineered aortic heart valves, it is necessary to gain insight into the effects of mechanical stimuli on the mechanical behavior of the tissue using mathematical models. In this study, a finite-element (FE) model is presented to relate changes in collagen fiber content and orientation to the mechanical loading condition within the engineered construct. We hypothesized that collagen fibers aligned with principal strain directions and that collagen content increased with the fiber stretch. The results indicate that the computed preferred fiber directions run from commissure to commissure and show a strong resemblance to experimental data from native aortic heart valves.

2007 ◽  
Vol 129 (6) ◽  
pp. 880-889 ◽  
Author(s):  
Hsiao-Ying Shadow Huang ◽  
Jun Liao ◽  
Michael S. Sacks

Within the aortic valve (AV) leaflet resides a population of interstitial cells (AVICs), which serve to maintain tissue structural integrity via protein synthesis and enzymatic degradation. AVICs are typically characterized as myofibroblasts, exhibit phenotypic plasticity, and may play an important role in valve pathophysiology. While it is known that AVICs can respond to mechanical stimuli in vitro, the level of in vivo AVIC deformation and its relation to local collagen fiber reorientation during the cardiac cycle remain unknown. In the present study, the deformation of AVICs was investigated using porcine AV glutaraldehyde fixed under 0–90mmHg transvalvular pressures. The resulting change in nuclear aspect ratio (NAR) was used as an index of overall cellular strain, and dependencies on spatial location and pressure loading levels quantified. Local collagen fiber alignment in the same valves was also quantified using small angle light scattering. A tissue-level finite element (FE) model of an AVIC embedded in the AV extracellular matrix was also used explore the relation between AV tissue- and cellular-level deformations. Results indicated large, consistent increases in AVIC NAR with transvalvular pressure (e.g., from mean of 1.8 at 0mmHg to a mean of 4.8 at 90mmHg), as well as pronounced layer specific dependencies. Associated changes in collagen fiber alignment indicated that little AVIC deformation occurs with the large amount of fiber straightening for pressures below ∼1mmHg, followed by substantial increases in AVIC NAR from 4mmHgto90mmHg. While the tissue-level FE model was able to capture the qualitative response, it also underpredicted the extent of AVIC deformation. This result suggested that additional micromechanical and fiber-compaction effects occur at high pressure levels. The results of this study form the basis of understanding transvalvular pressure-mediated mechanotransduction within the native AV and first time quantitative data correlating AVIC nuclei deformation with AV tissue microstructure and deformation.


Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 474
Author(s):  
Silvia Todros ◽  
Silvia Spadoni ◽  
Edoardo Maghin ◽  
Martina Piccoli ◽  
Piero G. Pavan

Muscular tissue regeneration may be enhanced in vitro by means of mechanical stimulation, inducing cellular alignment and the growth of functional fibers. In this work, a novel bioreactor is designed for the radial stimulation of porcine-derived diaphragmatic scaffolds aiming at the development of clinically relevant tissue patches. A Finite Element (FE) model of the bioreactor membrane is developed, considering two different methods for gripping muscular tissue patch during the stimulation, i.e., suturing and clamping with pliers. Tensile tests are carried out on fresh and decellularized samples of porcine diaphragmatic tissue, and a fiber-reinforced hyperelastic constitutive model is assumed to describe the mechanical behavior of tissue patches. Numerical analyses are carried out by applying pressure to the bioreactor membrane and evaluating tissue strain during the stimulation phase. The bioreactor designed in this work allows one to mechanically stimulate tissue patches in a radial direction by uniformly applying up to 30% strain. This can be achieved by adopting pliers for tissue clamping. Contrarily, the use of sutures is not advisable, since high strain levels are reached in suturing points, exceeding the physiological strain range and possibly leading to tissue laceration. FE analysis allows the optimization of the bioreactor configuration in order to ensure an efficient transduction of mechanical stimuli while preventing tissue damage.


2016 ◽  
Vol 8 (3) ◽  
pp. 5
Author(s):  
Jirí Stavek

<p class="1Body">An attempt is presented for the description of the spectral colors using the standard trigonometric tools in order to extract more information about photons. We have arranged the spectral colors on an arc of the circle with the radius R = 1 and the central angle θ = π/3 when we have defined cos (θ) = λ<sub>380</sub>/λ<sub>760</sub> = 0.5. Several trigonometric operations were applied in order to find the gravity centers for the scotopic, photopic, and mesopic visions. The concept of the center of gravity of colors introduced Isaac Newton. We have postulated properties of the long-lived photons with the new interpretation of the Hubble (Zwicky-Nernst) constant H<sub>0</sub> = 2.748… * 10<sup>-18</sup> kg kg<sup>-1 </sup>s<sup>-1</sup>, the specific mass evaporation rate (SMER) of gravitons from the source mass. The stability of international prototypes of kilogram has been regularly checked. We predict that those standard kilograms due to the evaporation of gravitons lost 8.67 μg kg<sup>-1</sup> century<sup>-1</sup>. The energy of long-lived photons was trigonometrically decomposed into three parts that could be experimentally tested: longitudinal energy, transverse energy and energy of evaporated gravitons. We tested the properties of the long-lived photons with the experimental data published for the best available standard candles: supernovae Type Ia. There was found a surprising match of those experimental data with the model of the long-lived photons. Finally, we have proposed a possible decomposition of the big G (Newtonian gravitational constant) and the small kappa κ (Einsteinian gravitational constant) in order to get a new insight into the mysterious gravitational force and/or the curvature concept.</p>


2018 ◽  
Vol 19 (12) ◽  
pp. 3858
Author(s):  
Milan Hodošček ◽  
Nadia Elghobashi-Meinhardt

A combination of molecular dynamics (MD) simulations and computational analyses uncovers structural features that may influence substrate passage and exposure to the active sites within the proteolytic chamber of the 20S proteasome core particle (CP). MD simulations of the CP reveal relaxation dynamics in which the CP slowly contracts over the 54 ns sampling period. MD simulations of the SyringolinA (SylA) inhibitor within the proteolytic B 1 ring chamber of the CP indicate that favorable van der Waals and electrostatic interactions account for the predominant association of the inhibitor with the walls of the proteolytic chamber. The time scale required for the inhibitor to travel from the center of the proteolytic chamber to the chamber wall is on the order of 4 ns, accompanied by an average energetic stabilization of approximately −20 kcal/mol.


2018 ◽  
Author(s):  
Minryung R. Song ◽  
Sang Wan Lee

AbstractDopamine activity may transition between two patterns: phasic responses to reward-predicting cues and ramping activity arising when an agent approaches the reward. However, when and why dopamine activity transitions between these modes is not understood. We hypothesize that the transition between ramping and phasic patterns reflects resource allocation which addresses the task dimensionality problem during reinforcement learning (RL). By parsimoniously modifying a standard temporal difference (TD) learning model to accommodate a mixed presentation of both experimental and environmental stimuli, we simulated dopamine transitions and compared it with experimental data from four different studies. The results suggested that dopamine transitions from ramping to phasic patterns as the agent narrows down candidate stimuli for the task; the opposite occurs when the agent needs to re-learn candidate stimuli due to a value change. These results lend insight into how dopamine deals with the tradeoff between cognitive resource and task dimensionality during RL.


Author(s):  
Kristin S. Miller ◽  
Brianne K. Connizzo ◽  
Elizabeth Feeney ◽  
Louis J. Soslowsky

One postulated mechanism of tendon structural response to mechanical load is collagen fiber re-alignment. Recently, where collagen fiber re-alignment occurs during a tensile mechanical test has been shown to vary by tendon age and location in a postnatal developmental mouse supraspinatus tendon (SST) model [1]. It is thought that as the tendon matures and its collagen fibril network, collagen cross-links and collagen-matrix interactions develop, its ability to respond quickly to mechanical stimuli hastens [1]. Additionally, the insertion site and midsubstance of postnatal SST may develop differently and at different rates, providing a potential explanation for differences in fiber re-alignment behaviors at the insertion site and midsubstance at postnatal developmental time points [1]. However, collagen fiber re-alignment behavior, in response to mechanical load at a mature age and in comparison to developmental ages, have not been examined. Therefore, the objectives of this study are to locally measure: 1) fiber re-alignment during preconditioning and tensile mechanical testing and 2) to compare local differences in collagen fiber alignment and corresponding mechanical properties to address tissue response to mechanical load in the mature and postnatal developmental mouse SST. We hypothesize that 1) 90 day tendons will demonstrate the largest shift in fiber re-alignment during preconditioning, but will also re-align during the toe- and linear-regions. Additionally, we hypothesize that 2) mechanical properties and initial collagen fiber alignment will be greater in the midsubstance of the tendon compared to the tendon-to-bone insertion site at 90 days, 3) that mechanical properties will increase with age, and that 4) collagen fiber organization at the insertion site will decrease with age.


Author(s):  
D R Absolom ◽  
W Zingg ◽  
A W Neumann ◽  
C J van Oss

It has been suggested that platelet phagocytosis might be a useful model to provide insight into platelet adhesion to polymer substrates commonly employed in biocompatibility studies. To test this supposition the present study of platelet engulfment of four strains of bacteria (opsonized as well as non-opsonized) under well defined in vitro physical conditions was undertaken. In physiologic conditions, platelet adhesion is maximum on the more hydrophilic polymers and minimum on the more hydrophobic surfaces; bacterial engulfment under the same conditions follows an identical pattern in that the more hydrophilic bacteria are more readily engulfed. The experimental data further suggest that, unlike phagocytosis by neutrophils platelet interaction with bacteria is non-specific in that it does not appear to be antibody receptor modulated. Opsonization of the bacteria does however play an important role in that it serves to increase the hydrophobicity of the bacteria thereby influencing the degree of bacterial engulfment. A striking correlation between the extent of bacterial engulfment and the Helmholtz Free Energy of Engulfment exists. Platelet adhesion to polymer substrates and platelet engulfment of bacteria appear to follow the same thermodynamic model.


Data in Brief ◽  
2019 ◽  
Vol 27 ◽  
pp. 104594
Author(s):  
Alaa Abbas ◽  
Felicite Ruddock ◽  
Rafid Alkhaddar ◽  
Glynn Rothwell ◽  
Iacopo Carnacina ◽  
...  

2002 ◽  
Vol 283 (5) ◽  
pp. E1084-E1101 ◽  
Author(s):  
Ahmad R. Sedaghat ◽  
Arthur Sherman ◽  
Michael J. Quon

We develop a mathematical model that explicitly represents many of the known signaling components mediating translocation of the insulin-responsive glucose transporter GLUT4 to gain insight into the complexities of metabolic insulin signaling pathways. A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate-1, activation of phosphatidylinositol 3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C-ζ is coupled with previously validated subsystem models of insulin receptor binding, receptor recycling, and GLUT4 translocation. A system of differential equations is defined by the structure of the model. Rate constants and model parameters are constrained by published experimental data. Model simulations of insulin dose-response experiments agree with published experimental data and also generate expected qualitative behaviors such as sequential signal amplification and increased sensitivity of downstream components. We examined the consequences of incorporating feedback pathways as well as representing pathological conditions, such as increased levels of protein tyrosine phosphatases, to illustrate the utility of our model for exploring molecular mechanisms. We conclude that mathematical modeling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signaling.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ritesh Ghosh ◽  
Ratnesh Chandra Mishra ◽  
Bosung Choi ◽  
Young Sang Kwon ◽  
Dong Won Bae ◽  
...  

AbstractSound vibration (SV) is considered as an external mechanical force that modulates plant growth and development like other mechanical stimuli (e.g., wind, rain, touch and vibration). A number of previous and recent studies reported developmental responses in plants tailored against SV of varied frequencies. This strongly suggests the existence of sophisticated molecular mechanisms for SV perception and signal transduction. Despite this there exists a huge gap in our understanding regarding the SV-mediated molecular alterations, which is a prerequisite to gain insight into SV-mediated plant development. Herein, we investigated the global gene expression changes inArabidopsis thalianaupon treatment with five different single frequencies of SV at constant amplitude for 1 h. As a next step, we also studied the SV-mediated proteomic changes in Arabidopsis. Data suggested that like other stimuli, SV also activated signature cellular events, for example, scavenging of reactive oxygen species (ROS), alteration of primary metabolism, and hormonal signaling. Phytohormonal analysis indicated that SV-mediated responses were, in part, modulated by specific alterations in phytohormone levels; especially salicylic acid (SA). Notably, several touch regulated genes were also up-regulated by SV treatment suggesting a possible molecular crosstalk among the two mechanical stimuli, sound and touch. Overall, these results provide a molecular basis to SV triggered global transcriptomic, proteomic and hormonal changes in plant.


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