Adsorption of Treponema Pallidum Protein to Functionalized Alkanethiol Self-Assembled Monolayers for Improving Biocompatibility

梅毒螺旋体蛋白吸附于功能化烷硫醇自组装单层膜上以改善生物相容性

• 批准号: 0705609
• 负责人: Kimberly Anderson
• 金额: $ 30.9万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0705609&HistoricalAwards=false
• 关键词: Adsorption; Treponema; Pallidum; Protein; Functionalized

This award to University of Kentucky by the Biomaterials program in the Division of Materials Research is to study the use of antigenic protein disguise to create biocompatible surfaces on blood-contacting medical devices. Clinical uses of blood-contacting devices are becoming more common. While many of these devices have been successfully used in patients for many years and are judged to be therapeutically beneficial, their performance is less than optimal. Upon implantation, some of these devices become completely coated with proteins and lead to formation of thrombi, which can cause significant problems. With this award, the PI will study binding of a bacterial protein called Tp0483 with human plasma fibronectin to create a hemocompatible surface by utilizing this as an antigenic disguise. The overall objective of this investigation is to study surface modifications by bacterial proteins called Tp0483, which as antigenic protein disguise may have potential applications in hemocompatible surfaces and systems. Earlier studies have shown that this bacterial protein binds with soluble dimeric fibronectin and the bound fibronectin serves an antigenic disguise for the bacterium. In this study, Tp0483 will be adsorbed to surfaces using self-assembled monolayer and the adsorption of fibronectin (FN) and a fibronectin fragment FN 7-10 will be investigated using surface plasmon resonance. In addition, the mechanism of adsorption of the FN and FN 7-10 to the Tp0483 will be studied using Atomic Force Microscopy (AFM) to determine binding strength of these proteins.Earlier, many different approaches have been used to create blood-compatible surfaces and while these processes have been shown to improve blood-compatibility, the creation of a wholly hemocompatible surface has, thus far, been unachievable. In this study, antigenic disguise will be used to create hemocompatible surfaces on implantable medical devices, and if successful, would have high impact in the use of these devices. In addition, information obtained on mechanisms of fibronectin binding to the bacterial protein TP0483 will provide a better understanding as to how the bacteria uses this protein for antigenic disguise. While this study focuses specifically on using the protein, Tp0483 for improving compatibility of blood-contacting materials, the results will form the basis for future studies where other naturally occurring proteins known for antigenic disguise can be studied. This award will provide graduate, undergraduate and high school students will opportunity to participate in this research and receive multidisciplinary training in engineering and materials science.

该奖项由材料研究部的生物材料项目授予肯塔基大学，旨在研究使用抗原蛋白伪装在血液接触的医疗设备上创建生物相容性表面。血液接触装置的临床使用变得越来越普遍。虽然许多这些设备已在患者身上成功使用多年，并被认为具有治疗效果，但它们的性能并非最佳。植入后，其中一些装置完全被蛋白质覆盖并导致血栓形成，这可能会导致严重的问题。凭借这一奖项，PI 将研究一种名为 Tp0483 的细菌蛋白与人血浆纤连蛋白的结合，利用其作为抗原伪装来创建血液相容性表面。这项研究的总体目标是研究名为 Tp0483 的细菌蛋白的表面修饰，其作为抗原蛋白伪装可能在血液相容性表面和系统中具有潜在应用。早期研究表明，这种细菌蛋白与可溶性二聚体纤连蛋白结合，结合的纤连蛋白为细菌提供了抗原伪装。 在本研究中，将使用自组装单层将 Tp0483 吸附到表面，并使用表面等离子体共振研究纤连蛋白 (FN) 和纤连蛋白片段 FN 7-10 的吸附。此外，将使用原子力显微镜 (AFM) 研究 FN 和 FN 7-10 吸附到 Tp0483 的机制，以确定这些蛋白质的结合强度。 早期，已使用许多不同的方法来创建血液相容性表面，虽然这些过程已被证明可以改善血液相容性，但迄今为止，完全血液相容性表面的创建尚未实现。在这项研究中，抗原伪装将用于在植入式医疗设备上创建血液相容性表面，如果成功，将对这些设备的使用产生重大影响。此外，获得的有关纤连蛋白与细菌蛋白 TP0483 结合机制的信息将有助于更好地了解细菌如何利用该蛋白进行抗原伪装。虽然这项研究特别侧重于使用蛋白质 Tp0483 来改善血液接触材料的相容性，但结果将构成未来研究的基础，可以研究其他已知的抗原伪装天然蛋白质。该奖项将为研究生、本科生和高中生提供参与这项研究并接受工程和材料科学多学科培训的机会。