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?.

生物材料计划在佐治亚理工学院材料研究部的这一职业奖是为了研究透明质酸（HA）材料和生物学功能之间的联系的机械理解。本研究将应用许多用于细胞生物学研究的高级微型特征技术，包括被动微流变学，光漂白后的荧光恢复，光学力量探针显微镜和渗透压研究。这些生物物理和软凝结物质工具将用于对两种主要类别HA蛋白系统的结构特性（网络结构，异质性，网格大小，捆绑，形状）和机械性能（可压缩性，损失和存储模量）的系统研究。在第一个推力中，模型HA-蛋白质溶液将用于研究与versican的相互作用，该蛋白在细胞外基质中发现的蛋白质以及推定的HA交联蛋白TSG-6，重链和PTX-3。第二个推力直接应对细胞周围涂层，这是锚定在许多细胞表面的HA-蛋白网络。最近的研究表明，HA蛋白结构的机械和地形特征赋予其生物环境中的各种结构和粘弹性特性，对细胞生理学和病理学（例如受精，细胞迁移，炎症，炎症和癌症转移）产生了深远的影响。总体而言，该项目有望在生物材料和细胞生物学方面提供非常基本的科学知识。作为宣传活动的一部分，这些研究将被整合到佐治亚理工学院的直接发现计划中，该计划使用佐治亚州的桃子网络高速互联网基础架构提供研究人员和教室之间的无缝视频会议，并与指定的教师在农村，社会经济学上培训的重要过程中与指定的教师紧密合作，以实现新的教学，以开发新的教学作品。功能 - 生理和病理学 - 例如软骨中的润滑液，人卵的受精，关节炎症和癌症的扩散。然而，对于这些各种透明质酸架构及其功能和特性知之甚少。使用新颖的工具和方法，该项目有望既可以提供对这种生物材料和细胞生物学的基本科学知识，同时又为其治疗用途的材料提供了新的见解。作为宣传计划的一部分，并与乡村，社会经济访问的社区中的指定老师紧密合作，该研究项目将集成到乔治亚技术学院的直接探索（D2D）计划中，该计划提供了研究人员和教室之间使用Georgia使用Georgia？Seam-Peach Net Internet Internet Internet Interfrastruct的无缝视频会议。将设计模块，以使用D2D技术将教师的演讲材料与对PIS实验室的访问相结合，从而为学生提供了探索细胞文化的机会，研究材料的粘弹性特性以及使用不同的实验工具？在达到教育目标的同时，学习主题，例如细胞的结构和功能？