The physiological role of airway smooth muscle

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Airway smooth muscle (ASM) is found all along the airway tree. Although its structure is elaborated and well defined, its elusive function has been perplexing the world's best physiologists for many decades. The present proposal is a renewal of an ongoing NSERC-funded program with the long-term objective to elucidate the physiological role of ASM. We have recently studied the dynamic behaviors of ASM using an in vitro setting that can mimic the ceaseless movements of the lungs during breathing. The results suggested that ASM serves to stabilize the caliber of the airways during breathing maneuvers. How this stabilizing function can be adjusted to accommodate greater ventilation, such as during a physical exercise, remains to be studied. In addition to pursue our in vitro investigations, we propose to broaden our scope by including experiments conducted in vivo in mice. Overall, we propose 2 short-term objectives. The 1st objective is to study in greater detail the stabilizing function of ASM in our in vitro setting that can mimic lung movements. The 2nd objective is to evaluate how the findings made in vitro affect the mechanics of the whole respiratory system in mice in vivo. The functional scheme of the program can be seen as a continuum, where the most promising findings made in vitro are subsequently investigated in vivo. Therefore, while new avenues are continuously explored in vitro, the work in vivo is motivated by our most important in vitro findings. A variety of methodologies are used. Since the contractility of ASM cannot be measured directly in vivo, we rely on cutting-edge technologies. These technologies are the products of many years of engineering, computational modeling and experimental biology. They now provide indirect measurements from which we can deduce the integrated role played by ASM in vivo. Some of the experiments we propose actually aim at exploiting the full capacity of these technologies to gain further insights on the intricate ways by which ASM influences the respiratory system. Our data set will also be exploited to further refine the computational models that are currently used in the field of respiratory mechanics to infer the role of ASM. The program is productive in terms of knowledge advancements, scientific publications and generation of new ideas and hypotheses. It is also conducive to important discoveries that have the potential to significantly change the field of respiratory mechanics. Finally, the program successfully trains highly qualified personnel (HQP) in a field that lies exactly at the interface between biology and engineering. More specifically, the HQP acquires the skills to scrutinize the behaviors of a mechanically active tissue in isolation, and to then study how these behaviors interact with other respiratory tissues to ultimately influence the function of the whole respiratory system.