A multiscale, spatially distributed model of asthmatic airway hyper-responsiveness |
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Authors: | Antonio Z. Politi Graham M. Donovan Merryn H. Tawhai Anne-Marie Lauzon James Sneyd |
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Affiliation: | a Department of Mathematics, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand b Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand c Department of Physiology, University of Massachusetts Medical School, Worcester, MA 01655, USA d Department of Medicine, Meakins-Christie Laboratories, McGill University, Montreal, Canada e Vermont Lung Center, Fletcher Allen Health Care, Department of Medicine, University of Vermont, Burlington, VT 05405, USA |
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Abstract: | We present a multiscale, spatially distributed model of lung and airway behaviour with the goal of furthering the understanding of airway hyper-responsiveness and asthma. The model provides an initial computational framework for linking events at the cellular and molecular levels, such as Ca2+ and crossbridge dynamics, to events at the level of the entire organ. At the organ level, parenchymal tissue is modelled using a continuum approach as a compressible, hyperelastic material in three dimensions, with expansion and recoil of lung tissue due to tidal breathing. The governing equations of finite elasticity deformation are solved using a finite element method. The airway tree is embedded in this tissue, where each airway is modelled with its own airway wall, smooth muscle and surrounding parenchyma. The tissue model is then linked to models of the crossbridge mechanics and their control by Ca2+ dynamics, thus providing a link to molecular and cellular mechanisms in airway smooth muscle cells. By incorporating and coupling the models at these scales, we obtain a detailed, computational multiscale model incorporating important physiological phenomena associated with asthma. |
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Keywords: | Crossbridge Calcium Tethering Smooth muscle cells Actin-myosin |
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