Modelling airway smooth muscle passive length adaptation via thick filament length distributions

Donovan, Graham M.

doi:10.1016/j.jtbi.2013.05.013

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…2 b). This can be viewed as a simplified version of the popular cross-bridge model for smooth muscle cells (30)(31)(32)(33)(34), with the unphosphorylated myosin motors disregarded. Myosin amounts for each of the states are indicated as m 0 , m 1 , and m 2 , respectively.…”

Section: Model Formulationmentioning

confidence: 99%

A Biomechanical Model for Fluidization of Cells under Dynamic Strain

Feng

2015

Biophysical Journal

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Recent experiments have investigated the response of smooth muscle cells to transient stretch-compress (SC) and compress-stretch (CS) maneuvers. The results indicate that the transient SC maneuver causes a sudden fluidization of the cell while the CS maneuver does not. To understand this asymmetric behavior, we have built a biomechanical model to probe the response of stress fibers to the two maneuvers. The model couples the cross-bridge cycle of myosin motors with a viscoelastic Kelvin-Voigt element that represents the stress fiber. Simulation results point to the sensitivity of the myosin detachment rate to tension as the cause for the asymmetric response of the stress fiber to the CS and SC maneuvers. For the SC maneuver, the initial stretch increases the tension in the stress fiber and suppresses myosin detachment. The subsequent compression then causes a large proportion of the myosin population to disengage rapidly from actin filaments. This leads to the disassembly of the stress fibers and the observed fluidization. In contrast, the CS maneuver only produces a mild loss of myosin motors and no fluidization.

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Section: Model Formulationmentioning

confidence: 99%

A Biomechanical Model for Fluidization of Cells under Dynamic Strain

Feng

2015

Biophysical Journal

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“…Previous studies have demonstrated length adaptation in isolated ASM strips under static (Pratusevich et al, 1995) and oscillatory , as well relaxed (Pratusevich et al, 1995) and contracted (McParland et al, 2005) conditions. A model of ASM adaptation under the dynamic conditions of breathing could be constructed by following prior methods (Donovan 2013), but at the expense of significantly complicating both the model, and limiting the possible analysis.…”

Section: Discussionmentioning

confidence: 99%

Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips

Dowie

Ansell²,

Noble³

et al. 2016

Respiratory Physiology & Neurobiology

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Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyperresponsiveness in asthma. Recent results by Ansell et al. (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that 1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways; 2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways; 3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway.

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“…Because the ASM length-tension relationship is key to this analysis, we also consider two variations of the cross-bridge model of Mijailovich et al (15), which offer extensions to account for length-tension measurements in ASM strips (e.g., Wang et al (19)): principally an empirical length-tension transfer function (e.g., Politi et al (20)) and an extension to the standard cross-bridge model that uses filament length distributions and binding site availability to generate the characteristic length-tension shape (21).…”

Section: Asm Cross-bridge Modelsmentioning

confidence: 99%

Airway Bistability Is Modulated by Smooth Muscle Dynamics and Length-Tension Characteristics

Donovan

2016

Biophysical Journal

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Airway closure has important implications for lung disease, especially asthma; in particular, the prospect of bistability between open and closed (or effectively closed) airway states has been thought to play a prominent role in airway closure associated with the formation of clustered ventilation defects in asthma. However, many existing analyses of closure consider only static airway equilibria; here we construct, to our knowledge, a new model wherein airway narrowing and closure dynamics are modulated by coupling the airway to cross-bridge models of airway smooth muscle dynamics and force generation. Using this model, we show that important qualitative features of airway pressure-radius hysteresis loops are highly dependent on both airway smooth muscle dynamics, and the length-tension relationship. Furthermore, we show that two recent experimental results from intact bronchial segments are both expressions of the same phenomenon: that a monotonically increasing lengthtension relationship, with sharply higher tension at longer lengths, is needed to drive the observed changes in low-compliance regions of the baseline pressure-radius curve. We also explore the potential implications of this finding for airway closure in coupled airway models.

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Modelling airway smooth muscle passive length adaptation via thick filament length distributions

Cited by 15 publications

References 23 publications

A Biomechanical Model for Fluidization of Cells under Dynamic Strain

A Biomechanical Model for Fluidization of Cells under Dynamic Strain

Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips

Airway Bistability Is Modulated by Smooth Muscle Dynamics and Length-Tension Characteristics

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