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The role of mathematical models in designing mechanopharmacological therapies for asthma

Irons, Linda; Brook, Bindi S.

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Authors

Linda Irons

BINDI BROOK BINDI.BROOK@NOTTINGHAM.AC.UK
Professor of Mathematical Medicine and Biology



Abstract

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 mechanophar-macology 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 bron-choconstriction 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 mechanopharmacolog-ical therapies in asthma, with discussion of how they could complement and accelerate current experimental approaches.

Journal Article Type Article
Acceptance Date Sep 7, 2022
Online Publication Date Oct 6, 2022
Publication Date Oct 6, 2022
Deposit Date Sep 21, 2022
Publicly Available Date Oct 6, 2022
Journal Frontiers in Systems Biology
Print ISSN 2674-0702
Electronic ISSN 2674-0702
Publisher Frontiers Media SA
Peer Reviewed Peer Reviewed
Volume 2
Article Number 929426
DOI https://doi.org/10.3389/fsysb.2022.929426
Keywords multiscale models; mechanobiology; biomechanics; hyperresponsiveness; re- modelling
Public URL https://nottingham-repository.worktribe.com/output/11466580
Publisher URL https://www.frontiersin.org/articles/10.3389/fsysb.2022.929426/full

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