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

职业：溶液中和细胞聚合物涂层中的透明质酸-蛋白质网络

• 批准号: 0955811
• 负责人: Jennifer Curtis
• 金额: $ 50万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0955811&HistoricalAwards=false
• 关键词: CAREER; Hyaluronan; Protein; Networks; Solution

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?.

该职业奖由佐治亚理工学院材料研究部生物材料项目颁发，旨在研究富含透明质酸 (HA) 的材料特性与生物功能之间联系的机制理解。本研究将应用一些在细胞生物学研究中很少使用的先进微观表征技术，包括被动微流变学、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态工具将用于系统研究两大类HA蛋白的结构特性（网络架构、异质性、网格尺寸、成束、形状）和机械特性（压缩性、损耗和储能模量）系统。第一个重点是，模型 HA 蛋白溶液将用于研究 HA 与多功能蛋白聚糖（一种在细胞外基质中发现的蛋白质）以及与假定的 HA 交联蛋白 TSG-6、重链和 PTX-3 的相互作用。第二个推力直接针对细胞周膜，即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多种结构和粘弹性特性，对细胞生理学和病理学（如受精、细胞迁移、炎症和癌症转移）产生深远的影响。总体而言，该项目预计将提供生物材料和细胞生物学方面非常基础的科学知识。作为外展活动的一部分，这些研究将被纳入佐治亚理工学院的 Direct to Discovery 计划，该计划使用佐治亚州的 Peach Net 高速互联网基础设施，在研究人员和教室之间提供无缝视频会议，并与指定教师密切合作在农村、社会经济弱势社区开发新的教学和培训模块。Hyalrunon 聚合物在许多身体功能（生理和病理）中发挥着重要作用，例如软骨中的润滑液、人体受精鸡蛋、关节炎症和癌症扩散。然而，人们对这些不同的透明质酸结构及其功能和特性知之甚少。使用新颖的工具和方法，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，同时为治疗用途已得到证实的材料提供新的见解。作为外展计划的一部分，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佐治亚理工学院的 Direct to Discovery (D2D) 计划，该计划在研究人员和研究人员之间提供无缝视频会议。教室使用佐治亚州的 Peach Net 高速互联网基础设施。模块的设计将教师的讲座材料与使用 D2D 技术对 PI 实验室的（虚拟）参观结合起来，让学生有机会探索细胞培养、研究材料的粘弹性特性以及使用不同的实验工具？同时达到学习“细胞的结构和功能”、“物质的本质”和“力的概念定律”等主题的教育目标。