Time variation, nonlinearity and heterogeneity mechanics of tissues: application to the respiratory system

This program of research is to explore analytically, computationally and experimentally the impact of nonstationarity in physiological systems on the analysis of oscillatory mechanics. It also aims to develop novel microtissue based system arrays, that enable the study of mechanobiology in tissue consisting of only 200-300 cells each. ******The approach to building the microtissue arrays is to use piezoelectric based material to form actuated posts in pairs embedded in a premade silicone mould for holding the tissues. The actuators oscillate and load the tissues over a range of frequencies and amplitude. ******We will develop this actuator system for ease of use for other researchers, and also we will use it to probe the microtissue time varying mechanical properties at the cell, tissue and whole lung level to investigate a recent discovery in my lab that has broad implications for understanding soft tissue mechanics.******We recently began exploring the impact of correctly accounting for time variation of mechanical properties of the respiratory system, and discovered a heretofore unknown relationship that can predict the well-established frequency dependence of resistance of lung tissue and the respiratory mechanics. This system behavior is currently attributed to the viscoelasticity of lung tissue or to heterogeneity amongst airway diameters. As such, the prediction from analysis of time-varying mechanics opens a new area of research of soft tissue mechanics, particularly in the lung where both resistance and elastance are known to be strongly time varying during breathing, particularly with airway obstruction. The theory may have deep implications as to the coupling of elastic and dissipative forces and nonlinear recruitment-derecruitment behavior during stretch and relaxation at the level of the cell, the tissue or the airway in the lung. ******We will use experimental measurements to validate and inform our lung models. This proposal includes training in several areas, including general systems analysis, mathematical modelling applied to physiological systems, signal and systems analysis including linear, nonlinear, heterogeneous and time variant systems. It also includes training in the measurement and understanding of soft tissue mechanics and mechanical behavior with a focus on the respiratory system. ******Significance: This program of research builds on the research in lung mechanics and lung tissue mechanical properties and physiology that founded my research career. If the predictions we are making in my lab are true, this work will represent my greatest contribution to lung mechanics and indeed to understanding of the mechanical properties of time-varying physiological systems in general. It has the potential to lead to a new conceptual framework for the frequency response of mechanical systems when the underlying mechanics are not stationary.