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）：界面处肽和蛋白质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，细胞培养物，组织工程结构等）中起着重要作用。在这里，我们提出了互补的表面生物分析和计算工具的互补套件，以在纳米级提供有关肽和蛋白质与表面的结构和相互作用的信息。最初将使用具有良好定义的A螺旋和B层二级结构的亮氨酸/赖氨酸（LK）肽来开发此工具集。研究的表面将从烷硫醇功能化的纳米颗粒到纳米结构底物。这些研究中使用的实验技术将包括固态NMR，静态飞行时间二级离子质谱法，总和频率产生，近边缘X射线吸收细胞良好结构，表面等离子体的共振和X射线光电学光谱。为了实现这些实验技术的全部力量，将开发互补的计算方法，以便使用分子动力学模拟来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一起将在纳米级，分子取向以及表面结合肽的侧链/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。然后，这些方法将扩展到更复杂的生物分子蛋白G的纳米级表征。该新工具集提供的信息将阐明在纳米级处于良好定义结构中将肽和蛋白质连接到表面上的设计原理，从而实现了蛋白质疗养和inmpobliption and Immbilitive和Immigobilization的分子级别控制。自从控制纳米级的表面固定肽和蛋白质的构象，取向等以来，这将在生物应用中产生广泛的影响，这将直接影响生物医学设备的生物活性和生物相容性。蛋白质和肽在纳米颗粒表面的附着是早期检测和治疗癌症的有前途的策略。同样，蛋白质和肽对生物医学设备的附着也有望改善这些设备的功能。本提案中开发的工具将提供最佳的蛋白质和肽所需的理解和信息。