A viscoelastic two-dimensional network model of the lung extracellular matrix

Iravani, Amin; Thambyah, Ashvin; Burrowes, Kelly

doi:10.1007/s10237-020-01336-1

Cited by 9 publications

(8 citation statements)

References 43 publications

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“…Our model also provides new insight into the roles that fibres and their recruitment play in determining bulk alveolar mechanics, and in particular how they ensure inflation stability to protect the alveolus from overdistension. In contrast with the traditional view that attributes alveolar inflation stability to the nonlinear stiffness behaviour of collagen fibres [15][16][17], we have demonstrated that stability can be achieved through linearly elastic but wavy collagen fibres that become progressively recruited into the load-bearing role as the alveolus inflates according to a waviness distribution that we observed experimentally (figure 2). The finite thickness of the alveolar wall is an important feature of our model because we show that inflation stability can be compromised by a decrease in the wall thickness-toradius ratio as well as by a decrease in collagen fibre stiffness.…”

Section: Discussioncontrasting

confidence: 99%

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Jawde

Karrobi

Roblyer

et al. 2021

J. R. Soc. Interface.

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Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related overdistension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibres, and investigate its pressure–volume behaviour under large deformations. Using second-harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to fit human pressure–volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 kPa and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibres are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio is greater than 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibres in healthy and diseased lungs.

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Section: Discussioncontrasting

confidence: 99%

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Jawde

Karrobi

Roblyer

et al. 2021

J. R. Soc. Interface.

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“…Numbers correspond to the following references: [1-8] Venegas et al, 2005;Tgavalekos et al, 2007;Winkler and Venegas, 2007;Bhatawadekar et al, 2015;Donovan, 2016;Leary et al, 2006;Donovan 2017;Foy et al, 2019. [9, 10] Choi et al, 2019Yoon et al, 2020[11-13] Berger et al, 2016Tawhai et al, 2004;Werner et al, 2009[14-17] Fredberg et al, 1997Wang et al, 2000;Bates et al, 2009;LaPrad et al, 2010[18, 19] Lavoie et al, 2012Pybus et al, 2021b[20-23] Fung, 1974Eskandari et al, 2019;Birzle et al, 2019;Hill et al, 2018[24-28] Mead et al, 1970, Cavalcante et al, 2005Iravani et al, 2020;Wellman et al, 2018;Oliveira et al, 2014[29, 30] Huh et al, 2010Kilic et al, 2019[31-33] Chernyavsky et al, 2014Chernyavsky et al, 2018;Pybus et al, 2021a [34] Lin et al, 2018[35, 36] Sun et al, 2005Smith et al, 2005 [37] Vargas et al, 2020 [38-43] Hai andMurphy, 1998;Mijailovich et al, 2000;Wang et al, 2008;Wang et al, 2010;Croisier et al, 2013;Croisier et al, 2015 [44] Irons et al, 2018 [45]…”

Section: Deep Inspiration and Tidal Breathing In Asthma: An Exemplarmentioning

confidence: 99%

The role of mathematical models in designing mechanopharmacological therapies for asthma

Irons

Brook

2022

Front. Syst. Biol.

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Healthy lung function depends on a complex system of interactions which regulate the mechanical and biochemical environment of individual cells to the whole organ. Perturbations from these regulated processes give rise to significant lung dysfunction such as chronic inflammation, airway hyperresponsiveness and airway remodelling characteristic of asthma. Importantly, there is ongoing mechanobiological feedback where mechanical factors including airway stiffness and oscillatory loading have considerable influence over cell behavior. The recently proposed area of mechanopharmacology recognises these interactions and aims to highlight the need to consider mechanobiology when identifying and assessing pharmacological targets. However, these multiscale interactions can be difficult to study experimentally due to the need for measurements across a wide range of spatial and temporal scales. On the other hand, integrative multiscale mathematical models have begun to show success in simulating the interactions between different mechanobiological mechanisms or cell/tissue-types across multiple scales. When appropriately informed by experimental data, these models have the potential to serve as extremely useful predictive tools, where physical mechanisms and emergent behaviours can be probed or hypothesised and, more importantly, exploited to propose new mechanopharmacological therapies for asthma and other respiratory diseases. In this review, we first demonstrate via an exemplar, how a multiscale mathematical model of acute bronchoconstriction in an airway could be exploited to propose new mechanopharmacological therapies. We then review current mathematical modelling approaches in respiratory disease and highlight hypotheses generated by such models that could have significant implications for therapies in asthma, but that have not yet been the subject of experimental attention or investigation. Finally we highlight modelling approaches that have shown promise in other biological systems that could be brought to bear in developing mathematical models for optimisation of mechanopharmacological therapies in asthma, with discussion of how they could complement and accelerate current experimental approaches.

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“…Further experimental work however, has revealed that collagen networks with connectivity slightly below the isostatic threshold, can also become rigid in the presence of large deformation instead, thus in such cases passive rigidity percolation may not be sufficient to explain ECM rigidity [44,85]. In particular, increasing shear deformation in sub-isostatic networks leads to nonlinear increase of the elastic modulus of such networks along different connectivity values, an observation highlighting the possibility of incorporating the active nature of such systems when applying rigidity percolation theory [139].…”

Section: Rigidity Percolation Probing Viscoelasticity Across Scalesmentioning

confidence: 99%

Viscoelastic Networks: Forming Cells and Tissues

Corominas-Murtra

Petridou

2021

Front. Phys.

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Spatiotemporal changes in viscoelasticity are a key component of the morphogenesis of living systems. Experimental and theoretical findings suggest that cellular- and tissue-scale viscoelasticity can be understood as a collective property emerging from macromolecular and cellular interactions, respectively. Linking the changes in the structural or material properties of cells and tissues, such as material phase transitions, to the microscopic interactions of their constituents, is still a challenge both at the experimental and theoretical level. In this review, we summarize work on the viscoelastic nature of cytoskeletal, extracellular and cellular networks. We then conceptualize viscoelasticity as a network theory problem and discuss its applications in several biological contexts. We propose that the statistical mechanics of networks can be used in the future as a powerful framework to uncover quantitatively the biomechanical basis of viscoelasticity across scales.

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A viscoelastic two-dimensional network model of the lung extracellular matrix

Cited by 9 publications

References 43 publications

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

Inflation instability in the lung: an analytical model of a thick-walled alveolus with wavy fibres under large deformations

The role of mathematical models in designing mechanopharmacological therapies for asthma

Viscoelastic Networks: Forming Cells and Tissues

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