Unraveling the Structural and Biomechanical Roles of Proteoglycans in Arterial Wall

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Proteoglycans (PGs) contribute to the basic development and maintenance of arteries. While other structural molecules and cells, such as the elastic fibers, smooth muscle cells, and collagen fibers have received extensive attention, little is known about the structural and biomechanical roles of PGs in arteries. This ignorance is likely linked to the low mass fraction of PGs, and that they are thought to be most important mechanically in resisting compressive stresses. Using natural chemicals that can dissolve away only the proteoglycans the investigators will measure the changes of artery stiffness as the proteoglycans are removed. Also, a mathematical model will be created that includes how the proteoglycans connect between the other molecules in the tissue understand and predict how the preoteoglycan's work to create tissue stiffness. There is a pressing need for such information in order to understand diseases of the arteries and heart. Undergraduate and graduate students who work in the project will learn to work with biology and mathematical theory to prepare them for careers in biomedical research.Given the complex interactions between PGs and other structural components, the overall goal of this research is to explore how PGs contribute to the structural and biomechanical integrity of arteries through coupled mechanical testing, advanced optical imaging, and microstructure-based constitutive modeling for charged hydrated tissues. With carefully designed experiments including local extracellular matrix structural and biochemical modification, this research takes a unique approach that integrates expertise in multi-photon microscopy, biaxial tensile testing, and structure-based mixture constitutive modeling to explore the contributions of PGs to the structural and biomechanical integrity of human arteries, and to understand alterations in structural and biomechanical roles of PGs in atherosclerosis. The important interplay between PGs and other extracellular matrix constituents will be incorporated into constitutive modeling by considering key structural information and osmotic effect. Results from the research will establish a solid foundation to investigate the mechanical roles of extracellular matrix constituents in the functionality of arteries, and launch quantitative mechanobiological understandings of vascular mechanics.