scholarly journals Local mechanical stimuli shape tissue growth in vertebrate joint morphogenesis

2021 ◽  
Author(s):  
Ester Comellas ◽  
Johanna E Farkas ◽  
Giona Kleinberg ◽  
Katlyn Lloyd ◽  
Thomas Mueller ◽  
...  
Keyword(s):  
Computational Models ◽  
Element Model ◽  
Light Sheet ◽  
Tissue Growth ◽  
Mechanical Stimuli ◽  
Local Tissue ◽  
Pressure Dynamics ◽  
Sense And Respond ◽  
Poroelastic Model ◽  
Experimental Findings

The correct formation of synovial joints is essential for proper motion throughout life. Movement-induced forces are critical to creating correctly shaped joints, but it is unclear how cells sense and respond to these mechanical cues. To determine how mechanical stimuli drive joint morphogenesis, we combined experiments on regenerating axolotl forelimbs with a poroelastic model of bone rudiment growth. Animals either regrew forelimbs normally (control) or were injected with a TRPV4 agonist to impair chondrocyte mechanosensitivity during joint morphogenesis. We quantified growth and shape in regrown humeri from whole mount light sheet fluorescence images of the regenerated limbs. Results revealed statistically significant differences in morphology and cell proliferation between the two groups, indicating that mechanical stimuli play a role in the shaping of the joint. Local tissue growth in our finite element model was dictated by a biological contribution, proportional to chondrocyte density, and a mechanical one, driven by fluid pore pressure dynamics. Computational predictions agreed with experimental outcomes, suggesting that interstitial pressure might promote local tissue growth. Predictive computational models informed by experimental findings allow us to explore potential physical mechanisms and regulatory dynamics involved in tissue growth to advance our understanding of the mechanobiology of joint morphogenesis.

scholarly journals Aspects of Uncertainty Analysis for Large Nonlinear Computational Models

2010 ◽  
Vol 24-25 ◽  
pp. 25-41 ◽  
Author(s):  
Keith Worden ◽  
W.E. Becker ◽  
Manuela Battipede ◽  
Cecilia Surace
Keyword(s):  
Finite Element ◽  
Monte Carlo ◽  
Computational Models ◽  
Element Model ◽  
Finite Element Models ◽  
Bayesian Algorithm ◽  
Basic Principles ◽  
Structure Interaction ◽  
Output Uncertainty ◽  
Input Uncertainties

This paper concerns the analysis of how uncertainty propagates through large computational models like finite element models. If a model is expensive to run, a Monte Carlo approach based on sampling over the possible model inputs will not be feasible, because the large number of model runs will be prohibitively expensive. Fortunately, an alternative to Monte Carlo is available in the form of the established Bayesian algorithm discussed here; this algorithm can provide information about uncertainty with many less model runs than Monte Carlo requires. The algorithm also provides information regarding sensitivity to the inputs i.e. the extent to which input uncertainties are responsible for output uncertainty. After describing the basic principles of the Bayesian approach, it is illustrated via two case studies: the first concerns a finite element model of a human heart valve and the second, an airship model incorporating fluid structure interaction.

scholarly journals Mechanosensitive calcium signaling promotes epithelial tight junction remodeling by activating RhoA

2021 ◽  
Author(s):  
Saranyaraajan Varadarajan ◽  
Rachel E. Stephenson ◽  
Eileen R. Misterovich ◽  
Jessica L. Wu ◽  
Ivan S. Erofeev ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intracellular Calcium ◽  
Tight Junctions ◽  
Calcium Influx ◽  
Cell Junctions ◽  
Mechanical Stimuli ◽  
Local Repair ◽  
Transient Activation ◽  
Epithelial Tight Junction ◽  
Sense And Respond

Epithelia maintain an effective barrier by remodeling cell-cell junctions in response to mechanical stimuli. Cells often respond to mechanical stress through activating RhoA and remodeling actomyosin. Previously, we found that local leaks in the barrier are rapidly repaired by localized, transient activation of RhoA – ″Rho flares″ – but how Rho flares are initiated remains unknown. Here, we discovered that intracellular calcium flashes occur in Xenopus laevis epithelial cells undergoing Rho flare-mediated remodeling of tight junctions. Calcium flashes originate at the site of barrier leaks and propagate into the cell. Depletion of intracellular calcium or inhibition of mechanosensitive calcium channels (MSC) reduced the amplitude of calcium flashes and diminished the activation of Rho flares. Furthermore, MSC-dependent calcium influx was necessary to maintain global barrier function by regulating local repair of tight junctions through efficient junction contraction. We propose that MSC-dependent calcium flashes are an important mechanism allowing epithelial cells to sense and respond to local leaks induced by mechanical stimuli.

The Use of a Cellular Strain Injury Criterion and Diffusion Tensor Imaging in a Computational Model of Traumatic Brain Injury

2010 ◽  
Author(s):  
Rika M. Wright ◽  
K. T. Ramesh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mechanical Loading ◽  
Computational Models ◽  
Diffusion Tensor ◽  
Diffuse Axonal Injury ◽  
Element Model ◽  
Cellular Level ◽  
Cellular Injury ◽  
Injury Mechanisms

With the increase in the number of soldiers sustaining traumatic brain injury from military incidents and the recent attention on sports related traumatic brain injury, there has been a focused effort to develop preventative and treatment methods for traumatic brain injury (TBI). Traumatic brain injury is caused by mechanical loading to the head, such as from impacts, sudden accelerations, or blast loading, and the pathology can range from focal damage in the brain to widespread diffuse injury [1]. In this study, we investigate the injury mechanisms of diffuse axonal injury (DAI), which accounts for the second largest percentage of deaths due to brain trauma [2]. DAI is caused by sudden inertial loads to the head, and it is characterized by damage to neural axons. Despite the extensive research on DAI, the coupling between the mechanical loading to the head and the damage at the cellular level is still poorly understood. Unlike previous computational models that use macroscopic stress and strain measures to determine injury, a cellular injury criterion is used in this work as numerous studies have shown that cellular strain can be related to the functional damage of neurons. The effectiveness of using this cellular injury criterion to predict damage in a finite element model of DAI is investigated.

Finite Element Analysis of Top-Hat–Stiffened Panels of Fiber-Reinforced–Plastic Boat Structures

2007 ◽  
Vol 44 (01) ◽  
pp. 16-26
Author(s):  
Ömer Eksik ◽  
R. Ajit Shenoi ◽  
Stuart S. J. Moy ◽  
Han Koo Jeong
Keyword(s):  
Finite Element ◽  
Lateral Pressure ◽  
Three Dimensional ◽  
Element Model ◽  
Stiffened Panel ◽  
Element Analysis ◽  
Stiffened Panels ◽  
Fiber Reinforced Plastic ◽  
Reinforced Plastic ◽  
Experimental Findings

This paper describes the development of a finite element model in order to assess the static response of a top-hat-stiffened panel under uniform lateral pressure. Systematic calculations were performed for deflection, strain, and stress using the developed model based on the ANSYS three-dimensional solid element (SOLID45). The numerical modeling results were compared to the experimental findings for validation and to further understand an internal stress pattern within the different constituents of the panel for explaining the likely causes of the panel failure. Good correlation between experimental and numerical strains and displacements was achieved.

scholarly journals The E. coli transcription factor GrlA is regulated by subcellular compartmentalization and activated in response to mechanical stimuli

2020 ◽  
Vol 117 (17) ◽  
pp. 9519-9528 ◽  
Author(s):  
Natalie Sirisaengtaksin ◽  
Max A. Odem ◽  
Rachel E. Bosserman ◽  
Erika M. Flores ◽  
Anne Marie Krachler
Keyword(s):  
Gastrointestinal Tract ◽  
Foodborne Pathogen ◽  
Virulence Gene ◽  
Adhesive Force ◽  
Mechanical Stimuli ◽  
Virulence Gene Expression ◽  
E Coli ◽  
Sense And Respond ◽  
Subcellular Compartmentalization ◽  
Enterocyte Effacement

Enterohemorrhagic Escherichia coli (EHEC) is a foodborne pathogen that colonizes the gastrointestinal tract and has evolved intricate mechanisms to sense and respond to the host environment. Upon the sensation of chemical and physical cues specific to the host’s intestinal environment, locus of enterocyte effacement (LEE)-encoded virulence genes are activated and promote intestinal colonization. The LEE transcriptional activator GrlA mediates EHEC’s response to mechanical cues characteristic of the intestinal niche, including adhesive force that results from bacterial adherence to epithelial cells and fluid shear that results from intestinal motility and transit. GrlA expression and release from its inhibitor GrlR was not sufficient to induce virulence gene transcription; mechanical stimuli were required for GrlA activation. The exact mechanism of GrlA activation, however, remained unknown. We isolated GrlA mutants that activate LEE transcription, independent of applied mechanical stimuli. In nonstimulated EHEC, wild-type GrlA associates with cardiolipin membrane domains via a patch of basic C-terminal residues, and this membrane sequestration is disrupted in EHEC that expresses constitutively active GrlA mutants. GrlA transitions from an inactive, membrane-associated state and relocalizes to the cytoplasm in response to mechanical stimuli, allowing GrlA to bind and activate the LEE1 promoter. GrlA expression and its relocalization in response to mechanical stimuli are required for optimal virulence regulation and colonization of the host intestinal tract during infection. These data suggest a posttranslational regulatory mechanism of the mechanosensor GrlA, whereby virulence gene expression can be rapidly fine-tuned in response to the highly dynamic spatiotemporal mechanical profile of the gastrointestinal tract.

Effect of cracks and pitting defects on gear meshing

2012 ◽  
Vol 226 (11) ◽  
pp. 2805-2815 ◽  
Author(s):  
Alfonso Fernandez del Rincon ◽  
Fernando Viadero ◽  
Miguel Iglesias ◽  
Ana de-Juan ◽  
Pablo Garcia ◽  
...  
Keyword(s):  
Finite Element ◽  
Computational Models ◽  
Inequality Constraints ◽  
Variable Stiffness ◽  
Element Model ◽  
Equation System ◽  
Transmission Error ◽  
Computational Effort ◽  
Gear Mesh ◽  
Non Linear

The development of vibration-based condition monitoring techniques, especially those focused on prognosis, requires the development of better computational models that enable the simulation of the vibratory behaviour of mechanical systems. Gear transmission vibrations are governed by the so-called gear mesh frequency and its harmonics, due to the variable stiffness of the meshing process. The fundamental frequency will be modulated by the appearance of defects which modify the meshing features. This study introduces an advanced model to assess the consequences of defects such as cracks and pitting on the meshing stiffness and other related parameters such as load transmission error or load sharing ratio. Meshing forces are computed by imposing the compatibility and complementarity conditions, leading to a non-linear equation system with inequality constraints. The calculation of deformations is subdivided into a global and a local type. The former is approached by a finite element model and the latter via a non-linear Herztian-based formulation. This procedure enables a reduced computational effort, in contrast to conventional finite element models with contact elements. The formulation used to include these defects is described in detail and their consequences are assessed by a quasi-static analysis of a transmission example.

A Study of Mechanosensing of an Osteoblast at Focal Adhesions Under Cyclic Strain Using Magnetic Micropillars

2019 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Kota Nagai
Keyword(s):  
Calcium Ion ◽  
Mechanical Vibration ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Mechanical Stimuli ◽  
Osteoblast Cells ◽  
Intracellular Calcium Ion ◽  
A Cell ◽  
Sense And Respond ◽  
Biochemical Signals

Abstract It has been reported that cells sense and respond to mechanical stimuli. Mechanical vibration promotes the cell proliferation and the cell differentiation of osteoblast cells at 12.5 Hz and 50 Hz, respectively. It indicates that osteoblast cells have a mechansensing system for mechanical vibration. There may be some mechanosensors and we focus on cellular focal adhesions through which mechanical and biochemical signals may be transmitted from extracellular matrices into a cell. However, it is very difficult to directly apply mechanical stimuli to focal adhesions. We developed a magnetic micropillar substrate on which micron-sized pillars are deflected according to applied magnetic field strength and focal adhesions adhering to the top surface of the pillars are given mechanical stimuli. In this paper, we focus on intracellular calcium ion as a second messenger of cellular mechanosensing and investigate the mechanosensing mechanism of an osteoblast cell at focal adhesions under cyclic strain using a magnetic micropillar substrate. The experimental results indicate that the magnetic micropillars have enough performance to response to an electric current applied to a coil in an electromagnet and to apply the cyclic strain of less than 3% to a cell. In the cyclic strain of less than 3%, the calcium response of a cell was not observed.

P2439Reconstructing electrocardiograms from computational models of infarcted ventricles to determine the location of myocardial infarct scars based on features of the signal

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y R Hill ◽  
J E Fieldsend ◽  
J R Terry
Keyword(s):  
Resting State ◽  
Computational Models ◽  
Myocardial Infarct ◽  
Element Model ◽  
Electrical Activation ◽  
Electrophysiological Properties ◽  
Ecg Signals ◽  
True Location ◽  
Characteristic Features ◽  
Reentrant Circuit

Abstract Myocardial infarction can cause ventricular tachycardia as a result of reentrant electrical activation waves propagating around the infarct scar. The tachycardia can be treated by radiofrequency catheter ablation which requires the cardiologist to deliver radiofrequency, via an intracardiac catheter, to ablate a specific site within the scar, disrupting the reentrant circuit, to terminate the arrhythmia. Therefore, determining the location of the scar is an important step in the procedure. MRI and CT scans can show the region of scar but are costly and are contraindicated in many cases. Cardiologists observe ECG recordings of the patient's tachycardia, looking at the gross characteristics of the signal to determine an approximate location of the scar. However, this technique assumes a recording of the patient's tachycardia is available, and is only able to suggest a gross region of the heart. In addition, the method is based on studies which have identified characteristic features of the ECG using intracardiac mapping to determine the location of the scar, which may be unreliable. This study aims to determine features of the ECG which may be able to predict the location of an infarct scar with more accuracy and specificity than current methods allow. The use of computational models ensures that the true location of the scar is known, unlike in previous studies. Moreover, we aim to determine whether there are any characteristics of resting state ECG which may indicate the location of an infarct scar. An anatomically accurate finite element model of rabbit ventricles in a conductive bath was utilised in order to simulate electrical activation waves and generate ECG signals, by reconstructing the extracellular potentials. Scar regions comprising of non-conducting scar surrounded by tissue with altered electrophysiological properties to represent the borderzone were incorporated into the ventricular model at varying locations across the myocardium. The models were stimulated using an S1S2 protocol to produce wave block and reentry. ECGs were reconstructed and the differences between models were observed. Results suggest that differences in timing and amplitude of the R wave on the ECG could be an indication of scar location. Changes in the repolarisation phase of the ECG were also apparent, suggesting more features which could determine the location of the scar. Importantly, characteristic features of the ECG could also be determined from resting state ECG, generated from models where scar was present but no reentry occurred. Utilising computational models of rabbit ventricles with scars incorporated at a variety of locations around the myocardium, we were able to determine a set of features from the ECG which may be of use in determining the location of an infarct scar. Future validation of this study using patient data could indicate that this methodology may be of use in predicting scar location in ablation procedures. Acknowledgement/Funding YH is funded by the MRC (MR/R024995/1). JT acknowledges the financial support of the EPSRC (EP/N014391/1) and the Wellcome Trust WT105618MA.

High Fidelity Computational Model of Bone Remodeling Cellular Mechanisms

2010 ◽  
Author(s):  
Charles L. Penninger ◽  
Andrés Tovar ◽  
Glen L. Niebur ◽  
John E. Renaud
Keyword(s):  
Bone Remodeling ◽  
Computational Models ◽  
Bone Adaptation ◽  
Daily Activities ◽  
High Fidelity ◽  
Mechanical Stimuli ◽  
Cellular Activity ◽  
Cellular Mechanisms ◽  
Mechanical Loads ◽  
Metabolic Activities

One of the most intriguing aspects of bone is its ability to grow, repair damage, adapt to mechanical loads, and maintain mineral homeostasis [1]. It is generally accepted that bone adaptation occurs in response to the mechanical demands of our daily activities; moreover, strain and microdamage have been implicated as potential stimuli that regulate bone remodeling [2]. Computational models have been used to simulate remodeling in an attempt to better understand the metabolic activities which possess the key information of how this process is carried out [3]. At present, the connection between the cellular activity of remodeling and the applied mechanical stimuli is not fully understood. Only a few mathematical models have been formulated to characterize the remolding process in terms of the cellular mechanisms that occur [4,5].

DEVELOPMENT AND BIOFIDELITY EVALUATION OF AN OCCUPANT BIOMECHANICAL MODEL OF A CHINESE 50TH PERCENTILE MALE FOR SIDE IMPACT

2017 ◽  
Vol 17 (07) ◽  
pp. 1740039 ◽  
Author(s):  
ZHENGWEI MA ◽  
LELE JING ◽  
FENGCHONG LAN ◽  
JINLUN WANG ◽  
JIQING CHEN
Keyword(s):  
Finite Element ◽  
Human Body ◽  
Computational Models ◽  
Rating Scale ◽  
Element Model ◽  
Side Impact ◽  
Body Parts ◽  
Lateral Impact ◽  
Human Body Model ◽  
Body Model

Finite element modeling has played a significant role in the study of human body biomechanical responses and injury mechanisms during vehicle impacts. However, there are very few reports on similar studies conducted in China for the Chinese population. In this study, a high-precision human body finite element model of the Chinese 50th percentile male was developed. The anatomical structures and mechanical characteristics of real human body were replicated as precise as possible. In order to analyze the model’s biofidelity in side-impact injury prediction, a global technical standard, ISO/TR 9790, was used that specifically assesses the lateral impact biofidelity of anthropomorphic test devices (ATDs) and computational models. A series of model simulations, focusing on different body parts, were carried out against the tests outlined in ISO/TR 9790. Then, the biofidelity ratings of the full human body model and different body parts were evaluated using the ISO/TR 9790 rating method. In a 0–10 rating scale, the resulting rating for the full human body model developed is 8.57, which means a good biofidelity. As to different body parts, the biofidelity ratings of the head and shoulder are excellent, while those of the neck, thorax, abdomen and pelvis are good. The resulting ratings indicate that the human body model developed in this study is capable of investigating the side-impact responses of and injuries to occupants’ different body parts. In addition, the rating of the model was compared with those of the other human body finite element models and several side-impact dummy models. This allows us to assess the robustness of our model and to identify necessary improvements.

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