The theme of this program project is pulmonary mechanics at the levels of tissue, cell and molecule. Each component project of this program deals with an innovative hypothesis regarding biophysical mechanisms of parenchymal function at each of these levels, the connections between levels and their alterability in selective but biologically important departures from the normal state. These projects deal with deformation and transit of neutrophils in the lung, disruption of surfactant function, mechanics of luminal narrowing of small airways, mechanics of the intraparenchymal contractile apparatus and, finally, the resistance of the adherent cell to shape distortion. In each component project physiological measurements are made, in many cases using novel technologies, and interpreted through the use of analytical and computational models. For example, to the degree that physical forces play a fundamental role in regulation of cellular functions, the combination of a unique experimental tool (magnetic twisting cytometry) and a novel, unifying hypothesis (the distending stress as the source of shape stability) leads the way to an exceptional opportunity to probe poorly defined regulatory pathways and their mechanisms of action. Our approach is multidisciplinary, involving investigators knowledgeable in respiratory physiology, the biology of chemical mediators, thoracic disease, cell biology, physics, engineering mechanics, instrumentation, mathematics and computer science. Collectively, the projects of this program address the cascade of events that culminate in normal or abnormal architecture, mechanics and gas transport.
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