The Role of Mechanical Tension in Neurons

2010 ◽  
Vol 1274 ◽  
Author(s):  
Taher Saif ◽  
Jagannathan Rajagopalan ◽  
Alireza Tofangchi
Keyword(s):  
Mechanical Response ◽  
Mechanical Forces ◽  
Active Tension ◽  
Mechanical Tension ◽  
Deformation Response ◽  
Linear Force ◽  
Tension Regulation ◽  
Over Time

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.

scholarly journals Role of neutrophils and α1-antitrypsin in coal- and silica-induced connective tissue breakdown

1999 ◽  
Vol 276 (2) ◽  
pp. L269-L279 ◽  
Author(s):  
K. Zay ◽  
S. Loo ◽  
C. Xie ◽  
D. V. Devine ◽  
J. Wright ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Hplc Analysis ◽  
Lavage Fluid ◽  
Dust Exposure ◽  
Mineral Dusts ◽  
Methionine Residues ◽  
Over Time ◽  
Rapid Appearance

Mineral dusts produce emphysema, and administration of dust to rats results in the rapid appearance of desmosine and hydroxyproline in lavage fluid, confirming that dusts directly induce connective tissue breakdown. To examine the role of neutrophils and α1-antitrypsin (α1-AT) in this process, we instilled silica or coal into normal rats or rats that had been pretreated with antiserum against neutrophils. One day after dust exposure, lavage fluid neutrophils and desmosine and hydroxyproline levels were all elevated; treatment with antiserum against neutrophils reduced neutrophils by 75%, desmosine by 40–50%, and hydroxyproline by 25%. By 7 days, lavage fluid neutrophils and desmosine level had decreased, whereas macrophages and hydroxyproline level had increased. By ELISA analysis, lavage fluid α1-AT levels were increased four- to eightfold at both times. On Western blot, some of the α1-AT appeared as degraded fragments, and by HPLC analysis, 5–10% of the methionine residues were oxidized. At both times, lavage fluid exhibited considerably elevated serine elastase inhibitory capacity and also showed elevations in metalloelastase activity. We conclude that, in this model, connective tissue breakdown is initially driven largely by neutrophil-derived proteases and that markedly elevated levels of functional α1-AT do not prevent breakdown, thus providing in vivo support for the concept of quantum proteolysis proposed by Liou and Campbell (T. G. Liou and E. J. Campbell. Biochemistry 34: 16171–16177, 1995). Macrophage-derived proteases may be of increasing importance over time, especially in coal-treated animals.

scholarly journals Modelling approaches for evaluating multiscale tendon mechanics

2016 ◽  
Vol 6 (1) ◽  
pp. 20150044 ◽  
Author(s):  
Fei Fang ◽  
Spencer P. Lake
Keyword(s):  
Computational Models ◽  
Mechanical Response ◽  
Helical Structure ◽  
Mechanical Analysis ◽  
Hierarchical Organization ◽  
Organization Model ◽  
Tendon Mechanics ◽  
Modelling Approaches

Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determined by its complicated hierarchical structure and varying amounts/organization of different tissue constituents. Although extensive research has been conducted to use modelling approaches to interpret tendon structure–function relationships in combination with experimental data, many issues remain unclear (i.e. the role of minor components such as decorin, aggrecan and elastin), and the integration of mechanical analysis across different length scales has not been well applied to explore stress or strain transfer from macro- to microscale. This review outlines mathematical and computational models that have been used to understand tendon mechanics at different scales of the hierarchical organization. Model representations at the molecular, fibril and tissue levels are discussed, including formulations that follow phenomenological and microstructural approaches (which include evaluations of crimp, helical structure and the interaction between collagen fibrils and proteoglycans). Multiscale modelling approaches incorporating tendon features are suggested to be an advantageous methodology to understand further the physiological mechanical response of tendon and corresponding adaptation of properties owing to unique in vivo loading environments.

Force-dependent vinculin binding to talin in live cells: a crucial step in anchoring the actin cytoskeleton to focal adhesions

2014 ◽  
Vol 306 (6) ◽  
pp. C607-C620 ◽  
Author(s):  
Hiroaki Hirata ◽  
Hitoshi Tatsumi ◽  
Chwee Teck Lim ◽  
Masahiro Sokabe
Keyword(s):  
Actin Cytoskeleton ◽  
Focal Adhesions ◽  
Living Cells ◽  
Live Cells ◽  
Mechanical Forces ◽  
Actin Network ◽  
Crucial Step

Mechanical forces play a pivotal role in the regulation of focal adhesions (FAs) where the actin cytoskeleton is anchored to the extracellular matrix through integrin and a variety of linker proteins including talin and vinculin. The localization of vinculin at FAs depends on mechanical forces. While in vitro studies have demonstrated the force-induced increase in vinculin binding to talin, it remains unclear whether such a mechanism exists at FAs in vivo. In this study, using fibroblasts cultured on elastic silicone substrata, we have examined the role of forces in modulating talin-vinculin binding at FAs. Stretching the substrata caused vinculin accumulation at talin-containing FAs, and this accumulation was abrogated by expressing the talin-binding domain of vinculin (domain D1, which inhibits endogenous vinculin from binding to talin). These results indicate that mechanical forces loaded to FAs facilitate vinculin binding to talin at FAs. In cell-protruding regions, the actin network moved backward over talin-containing FAs in domain D1-expressing cells while it was anchored to FAs in control cells, suggesting that the force-dependent vinculin binding to talin is crucial for anchoring the actin cytoskeleton to FAs in living cells.

Strength Retention of a New Microbial Cellulose Scaffold and Existing Collagen-Based Scaffolds After In Vivo Implantation in a Rabbit Model

2009 ◽  
Author(s):  
Michael I. Dishowitz ◽  
Miltiadis H. Zgonis ◽  
Jeremy J. Harris ◽  
Constance Ace ◽  
Louis J. Soslowsky
Keyword(s):  
Mechanical Behavior ◽  
Healing Process ◽  
Rabbit Model ◽  
In Vivo Model ◽  
Microbial Cellulose ◽  
Poor Outcomes ◽  
Over Time ◽  
Pullout Loads

Rotator cuff tendon tears often require large tensions for repair [1] and these tensions are associated with poor outcomes including rerupture [2]. To address this, repairs are often augmented with collagen-based scaffolds. Microbial cellulose, produced by A. xylinum as a laminar non-woven matrix, is another candidate for repair augmentation [3]. An ideal augmentation scaffold would shield the repair site from damaging loads as they change throughout the healing process. Although the initial mechanical properties of clinically used scaffolds have been well characterized [4–6], their mechanical behavior following implantation is not known. As a result, the role of these scaffolds throughout the healing process remains unknown. Therefore, the objective of this study is to characterize the mechanical behavior of existing collagen-based scaffolds and a new, microbial cellulose scaffold over time using an in vivo model. We hypothesize that: 1) collagen-based scaffolds will show decreased stiffness (1a) and suture pullout loads (1b) over time when compared to initial values while the microbial cellulose scaffold will not; and 2) the collagen-based scaffolds will have decreased stiffness (2a) and suture pullout loads (2b) when compared to the new, microbial cellulose scaffold at all timepoints.

scholarly journals Piezo1 links mechanical forces to red blood cell volume

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stuart M Cahalan ◽  
Viktor Lukacs ◽  
Sanjeev S Ranade ◽  
Shu Chien ◽  
Michael Bandell ◽  
...  
Keyword(s):  
Blood Cell ◽  
Calcium Influx ◽  
Mechanical Stretch ◽  
Conditional Knockout ◽  
Volume Control ◽  
Mechanical Forces ◽  
Gardos Channel

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.

scholarly journals The Role of Notch Signaling in Mechanical-Tension Regulation of H2-Calponin Gene

2013 ◽  
Vol 104 (2) ◽  
pp. 328a
Author(s):  
Geoffrey Cady ◽  
Wenrui Jiang ◽  
J.-P. Jin
Keyword(s):  
Notch Signaling ◽  
Mechanical Tension ◽  
Tension Regulation

scholarly journals In-vivo analysis of thoracic mechanical response under belt loading: The role of body mass index in thorax stiffness

2013 ◽  
Vol 46 (5) ◽  
pp. 883-889 ◽  
Author(s):  
David Poulard ◽  
François Bermond ◽  
Sabine Compigne ◽  
Karine Bruyère
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Mechanical Response ◽  
In Vivo Analysis

Role of wall tension in hypoxic responses of isolated rat pulmonary arteries

1998 ◽  
Vol 275 (6) ◽  
pp. L1069-L1077 ◽  
Author(s):  
Masami Ozaki ◽  
Carol Marshall ◽  
Yoshikiyo Amaki ◽  
Bryan E. Marshall
Keyword(s):  
Pulmonary Arteries ◽  
Mechanical Stretch ◽  
Effective Concentration ◽  
Active Tension ◽  
Wall Tension ◽  
Subsequent Response ◽  
Isolated Rat

The changes in force developed during 40-min exposures to hypoxia (37 ± 1 mmHg) were recorded in large (0.84 ± 0.02-mm-diameter) and small (0.39 ± 0.01-mm-diameter) intrapulmonary arteries during combinations of mechanical wall stretch tensions (passive + active myogenic components), equivalent to transmural vascular pressures of 5, 15, 30, 50, and 100 mmHg, and active (vasoconstriction) tensions, stimulated by PGF2α in doses of 0, 25, 50, and 75% effective concentrations. Constriction was observed in all arteries during the first minute; however, at any active tension, the pattern of the subsequent response was a function of the stretch tension. At 5, 15, and 30 mmHg, the constriction decreased slightly at 5 min and then increased again to remain constrictor throughout. At 50 and 100 mmHg, the initial constriction was followed by persistent dilation. Hypoxic constrictor responses, most resembling those observed in lungs in vivo and in vitro, were observed when the mechanical stretch wall tension was equivalent to 15 or 30 mmHg and the dose of PGF2α was 25 or 50% effective concentration. These observations reconcile many apparently contradictory results reported previously.

Endothelin-receptor blockade does not alter closure of the ductus arteriosus

1998 ◽  
Vol 275 (5) ◽  
pp. H1620-H1626 ◽  
Author(s):  
Jeffrey R. Fineman ◽  
Yasushi Takahashi ◽  
Christine Roman ◽  
Ronald I. Clyman
Keyword(s):  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Receptor Blockade ◽  
Active Tension ◽  
In Vitro Effects ◽  
Ly 83583

Endothelin-1 (ET-1) is synthesized within the wall of the ductus arteriosus (DA) and is a potent constrictor of the DA in vitro. However, the role of endogenous ET-1 in closure of the DA at birth remains unclear. Therefore, we studied the effects of a selective ETA-receptor antagonist (PD-156707), or its vehicle, on DA closure in 13 late-gestation fetal lambs during the first 5 h after birth. We also studied the effects of ETA-receptor blockade on DA constriction induced by oxygen, indomethacin (a cyclooxygenase inhibitor), and LY-83583 (a soluble guanylate cyclase inhibitor) in vitro ( n = 9 ductus arteriosus rings). In vehicle-treated lambs in vivo, the DA constricted during the 5-h study period after birth: DA resistance increased (from 0.007 ± 0.01 to 3.406 ± 4.15 mmHg ⋅ ml−1 ⋅ min ⋅ kg−1; P < 0.05); the pressure gradient across the DA increased (from 1.4 ± 2.1 to 25.2 ± 9.4 mmHg; P < 0.05); and DA blood flow decreased (from 193.5 ± 48.0 to 19.3 ± 14.3 ml ⋅ kg−1 ⋅ min−1; P < 0.05). In vitro, the DA was constricted by exposure to 30% oxygen (23 ± 14% net active tension; P < 0.05), indomethacin (5 × 10−6 M, 22 ± 5% net active tension; P < 0.05), LY-83583 (10−5 M, 24 ± 10% net active tension; P < 0.05), and ET-1 (10−7 M, 19 ± 4% net active tension; P < 0.05). Although PD-156707 blocked both the in vivo and in vitro effects of exogenous ET-1, it had no effect on postnatal ductus constriction nor on in vitro ductus contractile responses to oxygen, indomethacin, or LY-83583. This study suggests that endogenous ET-1 does not play an important role in closure of the DA at birth.

scholarly journals Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4983
Author(s):  
Marta Correia de Sousa ◽  
Nicolas Calo ◽  
Cyril Sobolewski ◽  
Monika Gjorgjieva ◽  
Sophie Clément ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mouse Liver ◽  
Potential Therapeutic Target ◽  
Stat3 Signaling ◽  
Gene And Protein Expression ◽  
Genetic Deletion ◽  
Almost All ◽  
Over Time

The microRNA 21 (miR-21) is upregulated in almost all known human cancers and is considered a highly potent oncogene and potential therapeutic target for cancer treatment. In the liver, miR-21 was reported to promote hepatic steatosis and inflammation, but whether miR-21 also drives hepatocarcinogenesis remains poorly investigated in vivo. Here we show using both carcinogen (Diethylnitrosamine, DEN) or genetically (PTEN deficiency)-induced mouse models of hepatocellular carcinoma (HCC), total or hepatocyte-specific genetic deletion of this microRNA fosters HCC development—contrasting the expected oncogenic role of miR-21. Gene and protein expression analyses of mouse liver tissues further indicate that total or hepatocyte-specific miR-21 deficiency is associated with an increased expression of oncogenes such as Cdc25a, subtle deregulations of the MAPK, HiPPO, and STAT3 signaling pathways, as well as alterations of the inflammatory/immune anti-tumoral responses in the liver. Together, our data show that miR-21 deficiency promotes a pro-tumoral microenvironment, which over time fosters HCC development via pleiotropic and complex mechanisms. These results question the current dogma of miR-21 being a potent oncomiR in the liver and call for cautiousness when considering miR-21 inhibition for therapeutic purposes in HCC.

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