Abstract
With every breath, the dynamically changing mechanical pressures must work in unison with the cells and soft tissue structures of the lung to permit air to efficiently traverse the airway tree and undergo gas exchange in the alveoli. The influence of mechanics on cell and tissue function is becoming apparent, raising the question: how does the airway tree co-exist within its mechanical environment to maintain normal cell function throughout its branching structure of diminishing dimensions? We introduce a new mechanical design principle for the conducting airway tree in which mechanotransduction at the level of cells is driven to orchestrate airway wall structural changes that can best maintain a preferred mechanical microenvironment. To support this principle, we report in vitro radius-transmural pressure relations for a range of airway radii obtained from healthy bovine lungs and model the data using a strain energy function together with a thick-walled cylinder description. From this framework, we estimate circumferential stresses and incremental Young's moduli throughout the airway tree. Our results indicate that the conducting airways consistently operate within a preferred mechanical homeostatic state, termed mechanical homeostasis, that is characterized by a narrow range of circumferential stresses and Young's moduli. This mechanical homeostatic state is maintained for all airways throughout the tree via airway wall dimensional and mechanical relationships. As a consequence, cells within the airway walls throughout the airway tree experience similar oscillatory strains during breathing that are much smaller than previously thought. Finally, we discuss the potential implications of how the maintenance of mechanical homeostasis, while facilitating healthy tissue-level alterations necessary for maturation, may lead to airway wall structural changes capable of chronic asthma.
Highlights
The act of breathing creates a mechanical environment that pervades all structures in the lungs down to the molecular level [1]
This study asks the following question: What are the fundamental principles guiding the distribution of airway wall properties – in particular, airway wall thicknesses and airway wall material properties - throughout the conducting airway tree residing in a dynamic mechanical environment? Previous studies have examined airway tree design principles but have ignored both the dynamic mechanical forces to which the airway tree is perpetually subjected and the tissue-level biomechanical properties of the airway wall
Using experimental and modeling approaches, we show that the distribution of tissue-level biomechanical properties of the airway walls within the normal conducting airway tree is consistent with the existence of mechanical homeostasis
Summary
The act of breathing creates a mechanical environment that pervades all structures in the lungs down to the molecular level [1]. As a pressure difference across the lungs draws air through the airway tree for gas exchange, all airways dilate and transmit mechanical stresses and strains to their cellular constituents – including smooth muscle, epithelial, and fibroblast cells. All of these airway cell types reside within a complex bifurcating airway tree, and through mechanotransduction, they actively sense and respond to their mechanical environment [1,2,3]. A tree design based purely on optimizing gas transport through rigid pipes ignores the fact that breathing dynamics can produce mechanically-driven alterations in the cells and tissue of the airway walls. It is conceivable that these alterations would eventually modify the material properties and the caliber of the pipes themselves perhaps in a fashion destroying the underlying physical optimization related to gas transport [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
