Unraveling the Structural and Biomechanical Roles of Proteoglycans in Arterial Wall

蛋白聚糖（pg）有助于动脉的基本发育和维持。虽然其他结构分子和细胞，如弹性纤维、平滑肌细胞和胶原纤维已经得到了广泛的关注，但人们对pg在动脉中的结构和生物力学作用知之甚少。这种无知可能与pg的低质量分数有关，并且它们被认为是抵抗压应力的最重要的机械。研究人员使用只能溶解蛋白聚糖的天然化学物质，测量去除蛋白聚糖后动脉硬度的变化。此外，还将建立一个数学模型，包括蛋白聚糖如何与组织中的其他分子连接，了解和预测蛋白聚糖如何产生组织刚度。为了了解动脉和心脏疾病，迫切需要这些信息。参与该项目的本科生和研究生将学习生物学和数学理论，为他们从事生物医学研究做好准备。考虑到pg与其他结构组分之间复杂的相互作用，本研究的总体目标是通过耦合力学测试、先进的光学成像和基于微结构的带电水合组织本构模型，探索pg如何促进动脉的结构和生物力学完整性。通过精心设计的实验，包括局部细胞外基质结构和生化修饰，本研究采用独特的方法，结合多光子显微镜、双轴拉伸测试和基于结构的混合本构模型的专业知识，探索pg对人体动脉结构和生物力学完整性的贡献，并了解pg在动脉粥样硬化中的结构和生物力学作用。通过考虑关键结构信息和渗透效应，pg和其他细胞外基质成分之间的重要相互作用将被纳入本构模型。研究结果将为研究细胞外基质成分在动脉功能中的力学作用奠定坚实的基础，并对血管力学进行定量的力学生物学理解。

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.