A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm

Onur Kilic, Arum Yoon, Sagar R. Shah, Hwan Mee Yong, Alejandro Ruiz-Valls, Hao Chang, Reynold Panettieri, Stephen B. Liggett, Alfredo Quiñones-Hinojosa, Steven S. An, Andre Levchenko

Research output: Contribution to journalArticle

Abstract

In asthma, the contraction of the airway smooth muscle and the subsequent decrease in airflow involve a poorly understood set of mechanical and biochemical events. Organ-level and molecular-scale models of the airway are frequently based on purely mechanical or biochemical considerations and do not account for physiological mechanochemical couplings. Here, we present a microphysiological model of the airway that allows for the quantitative analysis of the interactions between mechanical and biochemical signals triggered by compressive stress on epithelial cells. We show that a mechanical stimulus mimicking a bronchospastic challenge triggers the marked contraction and delayed relaxation of airway smooth muscle, and that this is mediated by the discordant expression of cyclooxygenase genes in epithelial cells and regulated by the mechanosensor and transcriptional co-activator Yes-associated protein. A mathematical model of the intercellular feedback interactions recapitulates aspects of obstructive disease of the airways, which include pathognomonic features of severe difficult-to-treat asthma. The microphysiological model could be used to investigate the mechanisms of asthma pathogenesis and to develop therapeutic strategies that disrupt the positive feedback loop that leads to persistent airway constriction.

Original languageEnglish (US)
JournalNature Biomedical Engineering
DOIs
StatePublished - Jan 1 2019

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Bronchial Spasm
Gene expression
Muscle
Asthma
Gene Expression
Muscles
Smooth Muscle
Epithelial Cells
Molecular Models
Licensure
Prostaglandin-Endoperoxide Synthases
Constriction
Theoretical Models
Feedback
Compressive stress
Proteins
Genes
Mathematical models
Therapeutics
Chemical analysis

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Cite this

Kilic, Onur ; Yoon, Arum ; Shah, Sagar R. ; Yong, Hwan Mee ; Ruiz-Valls, Alejandro ; Chang, Hao ; Panettieri, Reynold ; Liggett, Stephen B. ; Quiñones-Hinojosa, Alfredo ; An, Steven S. ; Levchenko, Andre. / A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm. In: Nature Biomedical Engineering. 2019.
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A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm. / Kilic, Onur; Yoon, Arum; Shah, Sagar R.; Yong, Hwan Mee; Ruiz-Valls, Alejandro; Chang, Hao; Panettieri, Reynold; Liggett, Stephen B.; Quiñones-Hinojosa, Alfredo; An, Steven S.; Levchenko, Andre.

In: Nature Biomedical Engineering, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Yoon, Arum

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AU - Ruiz-Valls, Alejandro

AU - Chang, Hao

AU - Panettieri, Reynold

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AU - An, Steven S.

AU - Levchenko, Andre

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