BME PhD Prospectus Defense - Brian Harvey

2:00 pm on Tuesday, January 22, 2013
4:00 pm on Tuesday, January 22, 2013
44 Cummington St, Room 203
Dr. Kenneth R. Lutchen, Department of Biomedical Engineering (Advisor)
Dr. Bela Suki, Department of Biomedical Engineering
Dr. Paul Barbone, Department of Mechanical Engineering
Dr. David Kaczka, Harvard Medical School, Beth Israel Deaconess Medical Center, Adjunct Assistant Professor at Boston University Department of Biomedical Engineering

Title: “Mechanical Determinants of Intact Airway Responsiveness”

Airway smooth muscle (ASM) in vivo exists in a dynamic mechanical environment where it is continually subjected to fluctuations in stretch due to breathing as well as changes in underlying matrix composition and stiffness. ASM cells within the airway adapt to these conditions to maintain airway caliber, and dysfunction of this adaptation is thought to be one of the features that causes airway hyperresponsiveness in asthma. However, recent studies suggest that the response of isolated ASM to dynamic forces simulating breathing does not necessarily translate to an intact airway. The mechanical properties and strain experienced by the ASM cell embedded within an airway wall are unknown. We hypothesize that the reactivity of intact airways is modulated by the manner in which the local stiffness and composition of the airway wall controls the stresses and strains it experiences during breathing and bronchoconstriction. To test this, we first will quantify the effect of small and large transmural pressure fluctuations on intact airway luminal diameter. Next, we will develop an ultrasound elastography technique to quantify the distribution of deformations and mechanical properties throughout the airway wall. The mechanical properties will be registered to specific airway components with histological techniques. Finally, we will examine the role of airway remodeling in asthma through enzymatic degradation of extracellular components and their effect on airway reactivity and mechanical properties. Preliminary data suggest that the airway has spatially varying mechanical properties and that supraphysiological pressure oscillations are required to observe the beneficial effect of stretch observed at the ASM and in vivo level.