scholarly journals Structural and mechanical remodeling of the cytoskeleton maintains tensional homeostasis in 3D microtissues under acute dynamic stretch

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthew Walker ◽  
Pauline Rizzuto ◽  
Michel Godin ◽  
Andrew E. Pelling
Keyword(s):  
Tensional Homeostasis ◽  
Mechanical Remodeling ◽  
Dynamic Stretch

scholarly journals Structural and mechanical remodeling of the cytoskeleton maintains tensional homeostasis in 3D microtissues under acute dynamic stretch

2019 ◽  
Author(s):  
Matthew Walker ◽  
Pauline Rizzuto ◽  
Michel Godin ◽  
Andrew E. Pelling
Keyword(s):  
Mechanical Properties ◽  
Dynamic Mechanical Properties ◽  
Filamentous Actin ◽  
Softening Behavior ◽  
3D Matrix ◽  
Tensional Homeostasis ◽  
Mechanical Remodeling ◽  
Dynamic Stretch ◽  
Cytoskeletal Elements ◽  
Cells Cultured

AbstractWhen stretched, cells cultured on 2D substrates share a universal softening and fluidization response that arises from poorly understood remodeling of well-conserved cytoskeletal elements. It is known, however, that the structure and distribution of the cytoskeleton is profoundly influenced by the dimensionality of a cell’s environment. Therefore, in this study we aimed to determine whether cells cultured in a 3D matrix share this softening behavior and to link it to cytoskeletal remodeling. To achieve this, we developed a high-throughput approach to measure the dynamic mechanical properties of cells and allow for sub-cellular imaging within physiologically relevant 3D microtissues. We found that fibroblast, smooth muscle and skeletal muscle microtissues strain softened but did not fluidize, and upon loading cessation, they regained their initial mechanical properties. Furthermore, microtissue prestress decreased with the strain amplitude to maintain a constant mean tension. This adaptation under an auxotonic condition resulted in lengthening. A filamentous actin cytoskeleton was required, and responses were mirrored by changes to actin remodeling rates and visual evidence of stretch-induced actin depolymerization. Our new approach for assessing cell mechanics has linked behaviors seen in 2D cultures to a 3D matrix, and connected remodeling of the cytoskeleton to homeostatic mechanical regulation of tissues.

Indicial response functions of growth and remodeling of common bile duct postobstruction

2004 ◽  
Vol 286 (3) ◽  
pp. G420-G427 ◽  
Author(s):  
Quang Dang ◽  
Hans Gregersen ◽  
Birgitte Duch ◽  
Ghassan S. Kassab
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Wall Thickness ◽  
Time Course ◽  
Quantitative Description ◽  
Biliary Duct ◽  
Stress And Strain ◽  
Response Functions ◽  
Mechanical Remodeling ◽  
Scheduled Time

Biliary duct obstruction is an important clinical condition that stems from cholelithiasis, the neoplasm in the wall or, most commonly, gallbladder stones. The objective of this study is to understand the structural and mechanical remodeling of the common bile duct (CBD) postobstruction. Porcine CBD was ligated near the duodenum that increased the duct's pressure from 6.4 to 18.3 cmH2O in the first 12 h and to 30.7 cmH2O after 32 days. The remodeling process was studied after 3 h, 12 h, 2 days, 8 days, and 32 days ( n = 5 in each group) after obstruction. One additional animal in each group was sham operated. At each scheduled time, the time course of change of morphometry (diameter, length, wall thickness, etc.) and mechanical properties (stress, strain, etc.) was documented. It was found that the diameter increased by about threefold and the wall thickness of the CBD doubled in the 32-day group compared with the sham group ( P < 0.001). The stress and strain increased initially with increase in pressure but recovered to near the control values by day 32 due to the structural and mechanical adaptations. Hence, the net effect of the structural and mechanical remodeling is to restore the stress and strain to their homeostatic values. Furthermore, the strain recovers more rapidly and more completely than stress. Finally, the remodeling data were expressed mathematically in terms of indicial response functions (IRF), i.e., change of a particular feature of a CBD in response to a unit step change of the pressure. The IRF approach provides a quantitative description of the remodeling process in the CBD.

scholarly journals Tensional Homeostasis in Single Fibroblasts

2014 ◽  
Vol 107 (1) ◽  
pp. 146-155 ◽  
Author(s):  
Kevin D. Webster ◽  
Win Pin Ng ◽  
Daniel A. Fletcher
Keyword(s):  
Tensional Homeostasis

scholarly journals Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

2018 ◽  
Vol 314 (2) ◽  
pp. H246-H254 ◽  
Author(s):  
Evan A. Kempf ◽  
Korynne S. Rollins ◽  
Tyler D. Hopkins ◽  
Alec L. Butenas ◽  
Joseph M. Santin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Peripheral Artery Disease ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Peripheral Artery ◽  
Nerve Activity ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease ◽  
Dynamic Stretch

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.

Extra Force From Asynchronous Stimulation of Cat Soleus Muscle Results From Minimizing the Stretch of the Common Elastic Elements

2006 ◽  
Vol 96 (3) ◽  
pp. 1401-1405 ◽  
Author(s):  
Thomas G. Sandercock
Keyword(s):  
Low Frequency ◽  
Muscle Length ◽  
Test Frequency ◽  
The Common ◽  
Tension Curve ◽  
Ventral Roots ◽  
The Difference ◽  
Dynamic Stretch ◽  
Elastic Elements ◽  
Stimulation Of

Rack and Westbury showed that low-frequency asynchronous stimulation of a muscle produces greater force compared with synchronous stimulation. This study tested the hypothesis that the difference results from the dynamic stretch of the common elastic elements. In eight anesthetized cats, the soleus was attached to a servomechanism to control muscle length and record force. The ventral roots were divided into four bundles so each innervated approximately 1/4 of the soleus. The elasticity shared by each part of the muscle was estimated and the servomechanism programmed to compensate for its stretch. At each test frequency (5, 7.5, and 10 Hz), the muscle was stimulated by asynchronous stimulation, synchronous stimulation, summation of force with each part stimulated individually, and summation with each part stimulated individually and the servomechanism mimicking tendon stretch during asynchronous stimulation. Muscle length was isometric except for the last protocol. The observed differences were small. The greatest difference occurred during stimulation at 5 Hz with muscle length on the ascending limb of the length-tension curve. Here, the average forces, normalized by asynchronous force, were asynchronous, 100%; synchronous, 73%; summation, 110%; and summation with stretch compensation, 98%. The results support the hypothesis and suggest that the common elasticity can be used to predict force gains from asynchronous stimulation.

scholarly journals Cell–matrix interaction during strain-dependent remodelling of simulated collagen networks

2016 ◽  
Vol 6 (1) ◽  
pp. 20150069 ◽  
Author(s):  
Lazarina Gyoneva ◽  
Carley B. Hovell ◽  
Ryan J. Pewowaruk ◽  
Kevin D. Dorfman ◽  
Yoav Segal ◽  
...  
Keyword(s):  
Mechanical Stability ◽  
Theoretical Work ◽  
Collagen Fibres ◽  
Tissue Remodelling ◽  
Cell Network ◽  
Fibre Network ◽  
Cell Matrix ◽  
A Cell ◽  
Tensional Homeostasis ◽  
Strain Dependent

The importance of tissue remodelling is widely accepted, but the mechanism by which the remodelling process occurs remains poorly understood. At the tissue scale, the concept of tensional homeostasis, in which there exists a target stress for a cell and remodelling functions to move the cell stress towards that target, is an important foundation for much theoretical work. We present here a theoretical model of a cell in parallel with a network to study what factors of the remodelling process help the cell move towards mechanical stability. The cell-network system was deformed and kept at constant stress. Remodelling was modelled by simulating strain-dependent degradation of collagen fibres and four different cases of collagen addition. The model did not lead to complete tensional homeostasis in the range of conditions studied, but it showed how different expressions for deposition and removal of collagen in a fibre network can interact to modulate the cell's ability to shield itself from an imposed stress by remodelling the surroundings. This study also showed how delicate the balance between deposition and removal rates is and how sensitive the remodelling process is to small changes in the remodelling rules.

scholarly journals Bachmann bundle impairment following linear ablation of left anterior wall: impact on left atrial function

2020 ◽  
Author(s):  
Yanjuan Zhang ◽  
Fengming Wu ◽  
Yu Gao ◽  
Nan Wu ◽  
Gang Yang ◽  
...  
Keyword(s):  
Contractile Function ◽  
Anterior Wall ◽  
Activation Time ◽  
Linear Ablation ◽  
Measured Activation ◽  
Mechanical Remodeling ◽  
Activation Times ◽  
And Function ◽  
Bachmann Bundle

Background: We aimed to evaluate the effect of Bachmann bundle (BB) impairment on electrical and mechanical function of the left atrium (LA), as well as the long-term clinical impact of such impairment. Design: We measured activation time in the five LA walls in 56 patients with atrial fibrillation. LA reservoir, conduit, and contractile function were also evaluated. Patients were divided into two groups based on ablation strategy: the circumferential pulmonary vein isolation (CPVI) group and CPVI with anterior wall linear ablation (LAWA) group. Patients in the CPVI+LAWA group were divided into two sub-groups based on ECG differences following ablation: the BB impairment group and intact BB group. LA activation time and function were then compared between the ablation strategy groups and the CPVI+LAWA subgroups. Results: Patients in the CPVI+LAWA group exhibited longer activation times in the anterior and lateral walls of the LA, poorer LA synchrony, and reduced LA contractile and reservoir function when compared with those in the CPVI group. In the BB impairment subgroup, we observed a discrepancy between electrical/mechanical remodeling. Among five walls, activation time was longest in this region. BB impairment was also associated with reduced LA function. Conclusion: Significant changes in LA function and conductibility were observed in patients with anterior wall ablation, especially those with iatrogenic BB impairment.

Crimp length decreases in lax tendons due to cytoskeletal tension, but is restored with tensional homeostasis

2016 ◽  
Vol 35 (3) ◽  
pp. 573-579 ◽  
Author(s):  
Michael Lavagnino ◽  
Andrew E. Brooks ◽  
Anna N. Oslapas ◽  
Keri L. Gardner ◽  
Steven P. Arnoczky
Keyword(s):  
Cytoskeletal Tension ◽  
Tensional Homeostasis

Abstract 1087: Effects of Oral Gap Junction Conduction-Enhancing Antiarrhythmic Peptide GAP-134 on Experimental Atrial Fibrillation in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gabriel Laurent ◽  
Howard Leong-Poi ◽  
Gordon Moe ◽  
Xudong Hu ◽  
Petsy Pui-Sze So ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Electrophysiological Study ◽  
Placebo Treatment ◽  
Refractory Periods ◽  
Percent Change ◽  
Dog Model ◽  
Antiarrhythmic Peptide ◽  
The Mean ◽  
Mechanical Remodeling

Background: Abnormal intercellular communication caused by connexin dysfunction may promote atrial fibrillation (AF). Objective: To assess the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a new dog model of atrial cardiomyopathy. Methods and Results: Twenty four dogs underwent simultaneous atrioventricular pacing (2 weeks at 220 bpm, atrioventricular delay 0 ms), and were randomly assigned to placebo treatment (PACED-PLACEBO; 12 dogs) or oral GAP-134 (PACED-GAP 134; 12 dogs) (starting at day 0). Percent change in left atrial systolic area (Δ% LASA) from baseline to 2 weeks was calculated using trans-esophageal echocardiography. At 2 weeks, animals underwent an open chest electrophysiological study; conduction velocity (CV) when pacing at 150ms cycle length (CL), effective refractory periods (ERP) and AF vulnerability were measured. The mean plasma concentration of GAP-134 was 557 ± 239 nmol/L. GAP-134 increased CV (395.1 ± 63.2 vs 307.8 ± 54.6 mm/s, p<0.01), and shortened ERP at 200ms CL (104.0 ± 8.6 vs 112.8 ± 11.5 ms, P<0.05). GAP-134 significantly reduced AF inducibility [% burst attempts inducing AF] and maintenance [mean AF duration, number of episodes >10min] in dogs with less than 100% ΔLASA (n=5). In dogs with more structural remodeling (ΔLASA ≥100%, n=7), CV increased but AF inducibility was unaffected. Conclusions: Oral GAP-134 prevents CV slowing in a dog model of atrial cardiomyopathy, but attenuates AF inducibility and maintenance only in dogs with less mechanical remodeling.

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