Elastosis during airway wall remodeling explains multiple co-existing instability patterns

Abstract

Living structures can undergo morphological changes in response to growth and alterations in microstructural properties in response to remodeling. From a biological perspective, airway wall inflammation and airway elastosis are classical hallmarks of growth and remodeling during chronic lung disease. From a mechanical point of view, growth and remodeling trigger mechanical instabilities that result in inward folding and airway obstruction. While previous analytical and computational studies have focused on identifying the critical parameters at the onset of folding, few have considered the post-buckling behavior. All prior studies assume constant microstructural properties during the folding process; yet, clinical studies now reveal progressive airway elastosis, the degeneration of elastic fibers associated with a gradual stiffening of the inner layer. Here, we explore the influence of temporally evolving material properties on the post-bifurcation behavior of the airway wall. We show that a growing and stiffening inner layer triggers an additional subsequent bifurcation after the first instability occurs. Evolving material stiffnesses provoke failure modes with multiple co-existing wavelengths, associated with the superposition of larger folds evolving on top of the initial smaller folds. This phenomenon is exclusive to material stiffening and conceptually different from the phenomenon of period doubling observed in constant-stiffness growth. Our study suggests that the clinically observed multiple wavelengths in diseased airways are a result of gradual airway wall stiffening. While our evolving material properties are inspired by the clinical phenomenon of airway elastosis, the underlying concept is broadly applicable to other types of remodeling including aneurysm formation or brain folding.

Mechanical properties of the airway tree: heterogeneous and anisotropic pseudoelastic and viscoelastic tissue responses

“…Nevertheless, as this study considered nonbranching regions, the monopodial and bipodial airway structure of porcine vs. human airways is irrelevant, and the similarity between human and animal lung structure allows that qualitative inferences may be made (42,47). The onset of disease will likely cause variation in measured material properties: prior works have measured increased airway resistance and rigidity due to airway remodeling in chronic diseases (5,9,17,39). Additionally, although this study provides pseudoelastic and viscoelastic material values, and facilitates new insights into regional and directional differences in airway tissue behavior, the in vivo loading environment is substantially more complex, and the tissue response may exhibit coupling between loading directions.…”

“…The predictive capabilities of pulmonary mechanics computational models are limited by the unavailability of airwayspecific constitutive relations. Previous studies highlighted the need for relevant experimental data to inform physiological models, especially for the bronchial tree (17,45,48,57). Past studies extensively investigated the buckling and folding behavior of the airways due to inflammation and bronchoconstriction in diseases such as asthma and bronchitis, since the effect is directly tied to airway resistance (4,16,53).…”

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

“…The lung has been deemed a viscoelastic material given it exhibits static hysteresis and stress relaxation (Bayliss and Robertson, 1939;Mount, 1955;Butler, 1957). The remodeling of pulmonary tissues and change in viscoelastic properties are expected in pulmonary disease progression but the underlying mechanisms are still not understood (Suki et al, 2005;Suki and Bates, 2011;Eskandari et al, , 2016. Despite its importance, dated studies attempted to consider viscoelastic properties but were greatly limited to manual techniques and empirical descriptors (Mount, 1955;Butler, 1957;Hughes et al, 1959;Marshall and Widdicombe, 1961;Hildebrandt, 1969;Lorino et al, 1982); these experiments appear to have been done using a syringe pump, which make the measurements inaccurate and causes data loss (Robichaud et al, 2017).…”

Quantifying the relationship between cell division angle and morphogenesis through computational modeling

“…In particular, modeling can be used to connect cellular-scale mechanisms with events on the tissue scale (Lowengrub et al, 2010;Stolarska et al, 2009) and understand complex systems in vivo (Di Ventura et al, 2006). For example, computational models can be used to study changes in biological tissue during development (Giorgi et al, 2014;Lejeune et al, 2016), the progression of disease in the lungs (Eskandari et al, 2016) and cardiovascular system (Göktepe et al, 2010;Zohdi et al, 2004), tumor growth and progression towards cancer (Frieboes et al, 2010;Wise et al, 2008), and wound healing (Tepole and Kuhl, 2016;Tepole, 2016). Computational modeling can also be used to study fundamental mechanisms controlling tissue growth and cellular organization such as growth suppressing contact inhibition (Galle et al, 2009), monolayer growth and formation (Byrne and Drasdo, 2008;Galle et al, 2006), the relationship between stress and growth (Ambrosi et al, 2012), and differential adhesion (Hogeweg, 2000).…”