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Reduced biomechanical models for precision-cut lung-slice stretching experiments
Journal of Mathematical Biology ( IF 1.9 ) Pub Date : 2021-03-15 , DOI: 10.1007/s00285-021-01578-2
Hannah J Pybus 1 , Amanda L Tatler 2 , Lowell T Edgar 3 , Reuben D O'Dea 1 , Bindi S Brook 1
Affiliation  

Precision-cut lung-slices (PCLS), in which viable airways embedded within lung parenchyma are stretched or induced to contract, are a widely used ex vivo assay to investigate bronchoconstriction and, more recently, mechanical activation of pro-remodelling cytokines in asthmatic airways. We develop a nonlinear fibre-reinforced biomechanical model accounting for smooth muscle contraction and extracellular matrix strain-stiffening. Through numerical simulation, we describe the stresses and contractile responses of an airway within a PCLS of finite thickness, exposing the importance of smooth muscle contraction on the local stress state within the airway. We then consider two simplifying limits of the model (a membrane representation and an asymptotic reduction in the thin-PCLS-limit), that permit analytical progress. Comparison against numerical solution of the full problem shows that the asymptotic reduction successfully captures the key elements of the full model behaviour. The more tractable reduced model that we develop is suitable to be employed in investigations to elucidate the time-dependent feedback mechanisms linking airway mechanics and cytokine activation in asthma.



中文翻译:

用于精确切割肺切片拉伸实验的简化生物力学模型

精确切割的肺切片 (PCLS),其中嵌入肺实质内的活气道被拉伸或诱导收缩,是一种广泛使用的离体检测方法,用于研究支气管收缩以及最近哮喘气道中促重塑细胞因子的机械激活. 我们开发了一种非线性纤维增强生物力学模型,用于解释平滑肌收缩和细胞外基质应变硬化。通过数值模拟,我们描述了有限厚度 PCLS 内气道的应力和收缩反应,揭示了平滑肌收缩对气道内局部应力状态的重要性。然后,我们考虑模型的两个简化限制(膜表示和薄 PCLS 限制的渐近减少),这允许分析进展。与完整问题的数值解的比较表明,渐近简化成功地捕获了完整模型行为的关键要素。我们开发的更易于处理的简化模型适用于研究,以阐明在哮喘中将气道力学和细胞因子激活联系起来的时间依赖性反馈机制。

更新日期:2021-03-15
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