Nanoscale Investigation of Protein-Surface Interactions

蛋白质-表面相互作用的纳米级研究

• 批准号: 7350156
• 负责人: DAVID G CASTNER
• 金额: $ 53.97万
• 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/7350156
• 关键词: Adsorption; Amides; Amino Acids; Antibodies; Behavior; Binding; Biocompatible Materials; Biological; Biological Models; Carbon; Chemicals; Complex; Computational Technique; Computing Methodologies; Condition; Cultured Cells; Data; Dependence; Development; Devices; Diagnostic; Early Diagnosis; Elements; Frequencies; Future; G-substrate; Generations; Goals; Gold; Grant; Helix (Snails); Hydration status; Immobilization; Implant; Investigation; Isotope Labeling; Kinetics; Knowledge; Label; Leucine; Liquid substance; Lysine; Measurement; Measures; Mediating; Membrane Proteins; Methods; Modeling; Molecular; Molecular Conformation; Molecular Structure; Monitor; Nanotechnology; Nitrogen; Numbers; Peptides; Play; Positioning Attribute; Property; Protein Dynamics; Proteins; Range; Relative (related person); Relaxation; Research; Research Personnel; Resolution; Roentgen Rays; Role; Rotation; Sampling; Secondary Protein Structure; Side; Solid; Spectrometry, Mass, Secondary Ion; Spectrum Analysis; Stretching; Structure; Sum; Surface; Surface Plasmon Resonance; System; Techniques; Time; Tissue Engineering; Vertebral column; Water; absorption; analytical tool; base; biomaterial compatibility; cancer therapy; computerized tools; design; ear helix; functional group; globular protein; improved functioning; interfacial; molecular dynamics; molecular modeling; monolayer; nanomaterials; nanoparticle; nanoscale; nanoscience; nanostructured; peptide structure; programs; protein function; protein structure; quantum; research study; residence; scaffold; simulation; solid state; tool

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.

肽和蛋白质在界面上的相互作用和分子结构在生物学中起着重要的作用。 广泛的生物医学应用（植入的生物材料、诊断阵列、细胞培养、组织培养） 工程构造等）。在这里，我们提出了一个互补的表面套件的发展 生物分析和计算工具，以提供有关结构的纳米级信息， 肽和蛋白质与表面的相互作用。初始模型亮氨酸/赖氨酸（LK）肽具有良好的- 确定的a-螺旋和b-折叠二级结构将用于开发该工具集。表面 研究的范围将从烷基乙氧基化物官能化的纳米颗粒到纳米结构基底。的 在这些研究中使用的实验技术将包括固态NMR、静态飞行时间二次离子 质谱，和频产生，近边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。为了实现这些实验性的 技术，互补的计算方法将被开发，从理论上分析， 吸附行为的这些相同的系统使用分子动力学模拟。综合这些 实验和计算方法将提供一个全面的了解，在纳米级的 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。这些方法将 可以扩展到一个更复杂的生物分子，蛋白质G的纳米级表征。的信息 将阐明将肽和蛋白质附着在 在纳米尺度上具有明确结构的表面，能够在分子水平上控制蛋白质吸附 和固定。这将在生物学应用中具有广泛的影响，因为控制 纳米级的表面固定肽和蛋白质的构象、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。 将蛋白质和肽附着到纳米颗粒的表面是用于早期免疫的有前途的策略。 检测和治疗癌症。类似地，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。本提案中开发的工具将 提供将蛋白质和肽最佳附着到表面所需的理解和信息。