CAREER: Hyaluronan-Protein Networks in Solution and in the Polymer Coat of Cells

该职业奖由格鲁吉亚理工学院材料研究部的生物材料项目授予，旨在研究对富含透明质酸（HA）的材料的性质与生物功能之间联系的机械理解。本研究将应用一些在细胞生物学研究中很少使用的先进的微观表征技术，包括被动微观流变学、光漂白后的荧光恢复、光学力探针显微镜和渗透压研究。这些生物物理和软凝聚物工具将用于系统研究两大类HA-蛋白质系统的结构特性（网络结构、异质性、网格尺寸、捆绑、形状）和机械特性（可压缩性、损耗和储能模量）。在第一个推力中，模型HA-蛋白质溶液将用于研究HA与多功能蛋白聚糖（一种在细胞外基质中发现的蛋白质）的相互作用，以及与假定的HA交联蛋白TSG-6、重链和PTX-3的相互作用。第二次攻击直接攻击细胞周被，这是一种锚定在许多细胞表面的HA蛋白网络。最近的研究表明，HA-蛋白结构的机械和形貌特征赋予其生物环境各种各样的结构和粘弹性，对细胞生理学和病理学如受精、细胞迁移、炎症和癌症转移具有深远的影响。总体而言，该项目预计将提供生物材料和细胞生物学方面的非常基础的科学知识。作为推广活动的一部分，这些研究将被纳入格鲁吉亚理工学院的“直接发现”项目，该项目使用格鲁吉亚？Hyalrunon聚合物在许多生理和病理的身体功能中起着重要作用，如软骨中的润滑液、人类卵子的受精、关节炎症和癌症的扩散。然而，对这些不同的透明质酸结构及其功能和性质知之甚少。使用新的工具和方法，该项目预计将提供这种生物材料和细胞生物学的基础科学知识，同时提供新的见解，其治疗用途是公认的材料。作为推广计划的一部分，并与农村，社会经济弱势社区的指定教师密切合作，该研究项目将被纳入直接发现（D2 D）计划在格鲁吉亚技术研究所，提供无缝的视频会议之间的研究人员和教室使用格鲁吉亚？的Peach Net高速互联网基础设施。模块将被设计为联合收割机的教师？使用D2 D技术（虚拟）访问PI实验室的讲座材料，让学生有机会探索细胞培养，研究材料的粘弹性，并使用不同的实验工具？同时达到教育目标，学习主题，如？细胞的结构和功能?物质的本质？然后呢？力的概念定律？

This Career award by the Biomaterials program in the Division of Materials Research to Georgia Institute of Technology is to study the mechanistic understanding of the link between the properties of hyaluronan (HA)-rich materials and biological functions. A number of advanced micro-characterization techniques that are rarely used in cell biology studies will be applied in this study, including passive microrheology, fluorescence recover after photobleaching, optical force probe microscopy and osmotic pressure studies. These biophysical and soft condensed matter tools will be used for a systematic investigation of the structural properties (network architecture, heterogeneity, mesh size, bundling, shape) and mechanical properties (compressibility, loss and storage moduli) of two major categories of HA-protein systems. In a first thrust, model HA-protein solutions will be used to investigate HA interactions with versican, a protein found in the extracellular matrix, and with the presumptive HA crosslinking proteins TSG-6, heavy chain and PTX-3. The second thrust directly tackles the pericellular coat, a HA-protein network anchored to many cell surfaces. Recent studies have indicated that mechanical and topographical features of HA-protein structures imparts onto its biological environment a diverse range of structural and viscoelastic properties with far-reaching consequences for cell physiology and pathology such as fertilization, cell migration, inflammation, and cancer metastasis. Overall, this project is expected to provide both a very fundamental scientific knowledge in biomaterials and cell biology. As part of the outreach activities, these research studies will be integrated into the Direct to Discovery program at Georgia Tech that provides seamless video conferencing between researchers and classrooms using Georgia?s Peach Net high-speed internet infrastructure, and working closely with a designated teacher in a rural, socioeconomically-disadvantaged community to develop new teaching and training modules.Hyalrunon polymer plays an important role in many body functions - both physiological and pathological - such as lubricating fluid in cartilage, fertilization of human egg, joint inflammation and spread of cancer. Yet, very little is known about these various hyaluronan architectures, and their functions and properties. Using novel tool and approaches, this project is expected to provide both fundamental scientific knowledge of this biomaterial and cell biology, while simultaneously providing new insights to a material whose therapeutic use is well established. As part of the outreach program and working closely with a designated teacher in a rural, socioeconomically-disadvantaged community, this research project will be integrated into the Direct to Discovery (D2D) program at Georgia Institute of Technology that provides seamless video conferencing between researchers and classrooms using Georgia?s Peach Net high-speed internet infrastructure. Modules will be designed to combine the teacher?s lecture material with (virtual) visits to the PIs Lab using D2D technology, giving students an opportunity to explore cell culture, study viscoelastic properties of materials, and use of different experimental tools ? all the while reaching educational goals to learn topics such as the ?structure and function of cells?, ?nature of matter?, and ?conceptual laws of forces?.