Unraveling the Structural and Biomechanical Roles of Proteoglycans in Arterial Wall

蛋白多糖(PG)对动脉的基本发育和维持起着重要作用。尽管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受到广泛关注，但对PGs在动脉中的结构和生物力学作用知之甚少。这种忽视很可能与PG的低质量分数有关，而且它们被认为是抵抗压应力的最重要的机械因素。使用只能溶解蛋白多糖的天然化学物质，研究人员将测量当蛋白多糖被移除时动脉硬度的变化。此外，还将建立一个数学模型，其中包括蛋白多糖如何连接组织中的其他分子，以了解和预测前蛋白多糖如何产生组织硬度。为了了解动脉和心脏疾病，迫切需要这种信息。参与该项目的本科生和研究生将学习如何使用生物学和数学理论为他们在生物医学研究中的职业生涯做准备。鉴于PGs与其他结构组件之间的复杂相互作用，本研究的总体目标是通过耦合力学测试、先进的光学成像和带电水化组织的基于微观结构的本构建模来探索PGs如何对动脉的结构和生物力学完整性做出贡献。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，本研究采取了一种独特的方法，整合了多光子显微镜、双向拉伸测试和基于结构的混合物本构模型的专业知识，以探索PGs对人类动脉结构和生物力学完整性的贡献，并了解PGs在动脉粥样硬化中的结构和生物力学作用的变化。通过考虑关键的结构信息和渗透效应，PGs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，并启动对血管力学的定量机械生物学理解。

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.