Effects of Immediate Biochemcial Environments on the Structure and Function of Aortic Elastin

该奖项的研究目的是研究弹性蛋白在体外脂质相互作用和糖基化过程中结构和功能的变化。弹性蛋白是机体的主要结构蛋白之一，对调节生理变形、为血管提供弹性支撑至关重要。弹性蛋白的寿命非常长，但它可能会受到化学物质暴露的累积效应的损害。由弹性蛋白脂质相互作用和糖基化引起的最终产物或侧链修饰通过改变弹性蛋白的移动性而损害了弹性蛋白的机械性能。我们将研究主动脉弹性蛋白的弹性和粘弹性在直接生化环境影响下的变化。利用拉曼光谱和傅里叶红外光谱，探讨可能的纤维内和纤维外腔室变化的分子基础。建立多尺度力学生物学本构模型，综合力学载荷和生物化学环境的影响，预测弹性蛋白的宏观弹性和粘弹性性能。这些研究结果将促进我们对弹性蛋白力学在血管重构中的作用的理解。弹性蛋白力学性质的变化具有重要的医学和生理学意义。许多病理条件涉及弹性蛋白的显著重塑，从而改变了组织的机械和物理化学功能。了解分子水平变化和弹性蛋白的机械功能之间的关系是理解其在活生物系统中的表现所不可或缺的。这个项目广泛的跨学科性质将极大地有利于通过这个项目培养的本科生/研究生。研究成果将通过期刊出版物和会议报告传播，并将纳入本科/研究生教学。我们计划将几个工程活动整合到波士顿大学的拓展项目中。其目标是帮助年轻女学生建立自信和对科学与工程的热爱。

The research objective of this award is to study the structural and functional changes of elastin due to in vitro elastin lipid interactions and glycation. As one of the major structural proteins of the body, elastin is essential to accommodate physiological deformation and provide elastic support for blood vessels. Elastin is remarkably long lived, but it can suffer damage from the cumulative effects of chemical exposure. End products or side chain modifications resulting from elastin lipid interactions and glycation compromise the mechanical properties of elastin by altering elastin's mobility. Changes in the elastic and viscoelastic properties of aortic elastin due to the effects of immediate biochemical environments will be studied. The molecular basis of possible intra- and extrafibrillar compartment changes will be explored using Raman and FT-IR microspectroscopy. A multi-scale mechanobiological constitutive model will be created to incorporate the effects of mechanical loading and biochemical environment in predicting the macroscopic elastic and viscoelastic properties of elastin. Results from these studies will advance our understanding of the role of elastin mechanics in vascular remodeling. Changes in the mechanical properties of elastin have important medical and physiological consequences. Many pathological conditions involve significant remodeling of elastin and thus altered mechanical and physiochemical functions of tissues. Knowledge of the relationship between molecular level alterations and elastin's mechanical functionality is integral to understanding its performance in living biological systems. The broad interdisciplinary nature of this project will greatly benefit the undergraduate/graduate students trained through this project. Research results will be disseminated through journal publications and conference presentations, and will also be incorporated into undergraduate/graduate teaching. We plan to integrate several engineering activities into the outreach programs at Boston University. The goal is to help young women students build self-confidence and a love for science and engineering.