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

该奖项的研究目标是研究由于体外弹性蛋白、脂类相互作用和糖基化而导致的弹性蛋白的结构和功能变化。作为人体的主要结构蛋白之一，弹性蛋白对调节生理变形和为血管提供弹性支撑是必不可少的。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。由于弹性蛋白、脂类相互作用和糖基化而产生的最终产物或侧链修饰会改变弹性蛋白的流动性，从而影响弹性蛋白的机械性能。将研究由于即时生化环境的影响而引起的主动脉弹性蛋白弹性和粘弹性特性的变化。可能的纤维内室和纤维室外变化的分子基础将使用拉曼和FT-IR显微光谱进行探索。在预测弹性蛋白的宏观弹性和粘弹性性质时，将建立一个多尺度的力学生物本构模型，以包含机械载荷和生物化学环境的影响。这些研究的结果将促进我们对弹性蛋白力学在血管重塑中的作用的理解。弹性蛋白的力学性质的变化具有重要的医学和生理后果。许多病理情况包括显著的弹性蛋白重塑，从而改变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对于了解其在生物系统中的性能是不可或缺的。该项目广泛的跨学科性质将极大地惠及通过该项目培养的本科生/研究生。研究成果将通过期刊出版物和会议报告进行传播，并将纳入本科生/研究生教学。我们计划将几项工程活动整合到波士顿大学的外展项目中。其目标是帮助年轻的女学生建立自信和对科学和工程的热爱。

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.