Nanoscale Investigation of Protein-Surface Interactions

蛋白质-表面相互作用的纳米级研究

• 批准号: 7038736
• 负责人: DAVID G CASTNER
• 金额: $ 60.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-06 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7038736
• 关键词: bioengineering /biomedical engineering; bioinformatics; biomaterial interface interaction; computational biology; computer system design /evaluation; intermolecular interaction; leucine; lysine; mass spectrometry; model design /development; molecular dynamics; nanotechnology; nuclear magnetic resonance spectroscopy; photoelectron spectrometry; protein kinase; protein structure; protein structure function; surface coating; surface plasmon resonance; surface property; technology /technique development; water

DESCRIPTION (provided by applicant): The interactions and molecular structures of peptides and proteins at interfaces play an important role in a wide range of biomedical applications (implanted biomaterials, diagnostic arrays, cell cultures, tissue engineering constructs, etc.). Here we propose the development of a complementary suite of surface bioanalytical and computational tools to provide information at the nanoscale about the structures and interactions of peptides and proteins with surfaces. Initially model leucine/lysine (LK) peptides with well- defined a-helix and b-sheet secondary structures will be used to develop this tool set. The surfaces investigated will range from alkanethiol functionalized nanoparticles to nanostructured substrates. The experimental techniques used in these studies will include solid state NMR, static time-of-flight secondary ion mass spectrometry, sum frequency generation, near edge x-ray absorption fine structure, surface plasmon resonance and x-ray photoelectrdn spectroscopy. To realize the full power of these experimental techniques, complementary computational approaches will be developed to theoretically analyze the adsorption behavior of these same systems using molecular dynamics simulations. Together these experimental and computational methods will provide a comprehensive understanding at the nanoscale of the secondary structure, molecular orientation and side chain/surface interactions of surface bound peptides, and the role of interfacial water in the peptide/surface interactions and structures. Then, these methods will be extended to the nanoscale characterization of a more complex biomolecule, Protein G. The information provided by this new tool set will elucidate the design principles for attaching peptides and proteins on surfaces in well-defined structures at the nanoscale, enabling molecular-level control of protein adsorption and immobilization. This will have wide spread impact in biological applications since controlling the conformation, orientation, etc. of surface immobilized peptides and proteins at the nanoscale will directly effect bioactivity and biocompatibility of biomedical devices. The attachment of proteins and peptides to the surface of nanoparticles is a promising strategy for the early detection and treatment of cancer. Similarly, the attachment of proteins and peptides to biomedical devices holds the promise for improving the function of those devices. The tools developed in this proposal will provide understanding and information needed to optimally attach protein and peptides to surfaces.

描述（由申请人提供）：肽和蛋白质在界面处的相互作用和分子结构在广泛的生物医学应用（植入生物材料、诊断阵列、细胞培养、组织工程构建体等）中发挥着重要作用。在这里，我们建议开发一套互补的表面生物分析和计算工具，以提供有关肽和蛋白质与表面的结构和相互作用的纳米级信息。最初，具有明确 a 螺旋和 b 片二级结构的亮氨酸/赖氨酸 (LK) 肽模型将用于开发该工具集。研究的表面范围从烷硫醇功能化纳米颗粒到纳米结构基材。这些研究中使用的实验技术包括固态核磁共振、静态飞行时间二次离子质谱、和频生成、近边缘X射线吸收精细结构、表面等离子体共振和X射线光电子能谱。为了充分发挥这些实验技术的作用，将开发补充计算方法，利用分子动力学模拟从理论上分析这些相同系统的吸附行为。这些实验和计算方法将在纳米尺度上提供对表面结合肽的二级结构、分子取向和侧链/表面相互作用以及界面水在肽/表面相互作用和结构中的作用的全面理解。然后，这些方法将扩展到更复杂的生物分子蛋白质 G 的纳米级表征。这个新工具集提供的信息将阐明在纳米级以明确结构的表面附着肽和蛋白质的设计原理，从而使蛋白质吸附和固定的分子水平控制。这将对生物应用产生广泛的影响，因为在纳米尺度上控制表面固定化肽和蛋白质的构象、取向等将直接影响生物医学装置的生物活性和生物相容性。将蛋白质和肽附着在纳米颗粒表面是早期检测和治疗癌症的一种有前景的策略。同样，将蛋白质和肽附着到生物医学设备上有望改善这些设备的功能。该提案中开发的工具将提供将蛋白质和肽最佳地附着到表面所需的理解和信息。