Mechanotransduction, asthma and airway smooth muscle

Fabry, Ben; Fredberg, Jeffrey J.

doi:10.1016/j.ddmod.2007.12.003

Cited by 17 publications

(17 citation statements)

References 38 publications

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“…The idea that force and length adaptation of muscle may also be actively regulated by mechanochemical signalling processes has only quite recently gained widespread acceptance (35). The situation appears reversed when it comes to the mechanical responses in nonmuscle cells that have been almost exclusively attributed to mechanochemical signalling pathways.…”

Section: Discussionmentioning

confidence: 96%

Single-cell response to stiffness exhibits muscle-like behavior

Mitrossilis

Fouchard

Guiroy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Living cells sense the rigidity of their environment and adapt their activity to it. In particular, cells cultured on elastic substrates align their shape and their traction forces along the direction of highest stiffness and preferably migrate towards stiffer regions. Although numerous studies investigated the role of adhesion complexes in rigidity sensing, less is known about the specific contribution of acto-myosin based contractility. Here we used a custom-made single-cell technique to measure the traction force as well as the speed of shortening of isolated myoblasts deflecting microplates of variable stiffness. The rate of force generation increased with increasing stiffness and followed a Hill force-velocity relationship. Hence, cell response to stiffness was similar to muscle adaptation to load, reflecting the force-dependent kinetics of myosin binding to actin. These results reveal an unexpected mechanism of rigidity sensing, whereby the contractile acto-myosin units themselves can act as sensors. This mechanism may translate anisotropy in substrate rigidity into anisotropy in cytoskeletal tension, and could thus coordinate local activity of adhesion complexes and guide cell migration along rigidity gradients.mechanosensing | adaptation to load | cell migration | cell spreading | cell mechanics A s part of their normal physiological functions, most cells in the organism need to respond to mechanical stimuli such as deformations, forces, and the geometry and stiffness of the extracellular matrix (1, 2). Aberrant mechanical responsiveness is often associated with severe diseases, including cardiovascular disorders, asthma, fibrotic diseases, or cancer metastasis.Since the early 1980s, several techniques have been developed to characterize the forces generated by living cells (3-5) and to investigate the effect of the mechanical properties of twodimensional (2D) substrates (6-8). It was shown that cells are able to sense and respond to the rigidity of their surroundings. For instance, cells cultured on elastic substrates with a rigidity gradient preferably locomote towards stiffer regions and align their shape, their cytoskeletal structures, and their traction forces along the direction of highest stiffness (9-11). Moreover, it has been demonstrated that matrix rigidity could direct stem cells' lineage specification (12).It is generally assumed that rigidity sensing is based on mechanochemical signal-transduction pathways. The search for the mechanosensing element has generated numerous plausible candidates (reviewed in ref.2). The most prominent of them is the focal adhesion complex (13,14). These molecular assemblies consist of numerous proteins that are associated with integrin adhesion receptors (15) and provide the pathway of force transmission from the cytoskeleton to the extracellular matrix (16). Adhesion of integrins to extracellular matrix proteins triggers the formation of focal adhesions, their connection to actin, and the contraction of the cytoskeleton by myosin II (17-19). On a soft substrat...

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Section: Discussionmentioning

confidence: 96%

Single-cell response to stiffness exhibits muscle-like behavior

Mitrossilis

Fouchard

Guiroy

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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208

254

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“…In contrast, capnovolumetry displayed bronchoconstriction in response to a small dose of histamine during tidal breathing (1,23,24). The airway smooth muscle of normal subjects remained in the relaxing state when it was stretched during tidal breathing.…”

Section: Discussionmentioning

confidence: 95%

“…If FEV 1 decreased <20% calculated from the baseline value, the subject continued to receive next dose of histamine until a cumulative dose reached to 2.2 mg. The test was terminated if the subjects showed either severe dyspnoea or FEV 1 was reduced by ≥20% from baseline or the highest dose of histamine was reached followed by salbutamol to reverse the process.…”

Section: Methodsmentioning

confidence: 99%

“…Bronchial provocation tests, commonly with methacholine or histamine, are mainly used to demonstrate airway hyperresponsiveness in patients with airway disease (1). Forced expiratory volume in 1 s (FEV 1 ) is simple and reproducible, and is one of the most common methods used to assess airway constriction response, but it has a lower sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of capnovolumetry‐derived dead space parameters with pulmonary function test in normal adults using histamine provocation

Sun

Yan

Yang

2014

Clinical Respiratory J

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“…Aging is thought to negatively affect the ability of the respiratory system to respond to mechanical loading as the aging lung is more susceptible to pulmonary injury following mechanical ventilation (Nin et al, 2008). Aging also impairs the sensitivity and reactivity of airway smooth muscle to mechanical stimuli (An et al, 2007; Fabry and Fredberg, 2007). Likewise, the aging diaphragm not only exhibits a lower maximal isometric tension, but also an impaired ability to recover diaphragmatic force in response to unloading (Criswell et al, 2003).…”

Section: Effect Of Aging On Respiratory Mechanotransductionmentioning

confidence: 99%

Effect of aging on cellular mechanotransduction

Fannin

Rice

et al. 2011

Ageing Research Reviews

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Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, respiratory systems and skin.

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Mechanotransduction, asthma and airway smooth muscle

Cited by 17 publications

References 38 publications

Single-cell response to stiffness exhibits muscle-like behavior

Single-cell response to stiffness exhibits muscle-like behavior

Comparison of capnovolumetry‐derived dead space parameters with pulmonary function test in normal adults using histamine provocation

Effect of aging on cellular mechanotransduction

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