Formation, Hydration, and Structure of Biomolecules at the Protein-Surface Interface

蛋白质-表面界面生物分子的形成、水合和结构

• 批准号: 1807215
• 负责人: Lauren Webb
• 金额: $ 44万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807215&HistoricalAwards=false
• 关键词: Formation; Hydration; Structure; Biomolecules; Protein

Proteins provide an extraordinary range of structures, properties, and functions that could be used in the design and building of novel devices and materials. Long term, this research has implications on the development of implantable medical devices including artificial joints and valves. Critical for such applications is for the protein to be effectively integrated into the devices. To this end, there is interest in attaching peptides and proteins to non-biological surfaces and materials reliably. The interface between the biomolecules and surface has properties are related to, but quite distinct from, those of the biological components and of the original surface. The three-dimensional structure and resulting function of proteins linked to surfaces can be radically different than in solution. Defining these differences is challenging. The research group of Dr. Lauren Webb at the University of Texas at Austin is addressing these challenges using a multidisciplinary research program focused on the investigation of biomolecules on rationally-designed and precisely-prepared surfaces. Dr. Webb fosters the participation of high school students in research in her own laboratories. Special emphasis is placed on increasing recruiting efforts in Texas high schools so that the diversity of students engaged in research reflects the diversity of the population of Texas. Despite the fact that the integration of biological molecules with non-biological materials is an area of current scientific interest, the understanding of the differences between the structures and properties of biomolecules attached to surfaces versus biomolecules in solution is relatively limited. Dr. Webb's research addresses the lack of fundamental understanding of what happens to biomolecules such as peptides and proteins in these alternative, substrate-bound environments. Dr. Webb's laboratory is using a unique chemical platform and an advanced set of analytical tools to address these fundamental questions from both an experimental and computational perspective. Gold surfaces are chemically functionalized with the electron-transfer protein azurin and studies of the protein's function are aimed at exploring conditions under which the gold remains stable. The research elucidates the mechanism of nucleation and formation of fibrils from surface-bound strand peptides. It also examines the influence of hydration of nominally dry surface-bound protein on the protein's structure and function. The experimental results are leveraged towards the development, testing, and validation of computational methods that may accurately predict the structure of proteins and peptides attached to artificial surfaces. Dr. Webb's long-term goal is to advance of the chemical understanding of peptides and protein behavior at surfaces so that the understanding reaches similar accuracy and predictability when compared to what is currently possible for solution-phase systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

蛋白质提供了非常广泛的结构、性质和功能，可用于设计和制造新的设备和材料。从长远来看，这项研究对包括人工关节和瓣膜在内的植入式医疗设备的发展具有重要意义。对于这样的应用来说，关键是蛋白质能够有效地集成到设备中。为此，人们对将多肽和蛋白质可靠地附着在非生物表面和材料上感兴趣。生物分子和表面之间的界面具有与生物成分和原始表面的属性相关但完全不同的属性。连接到表面的蛋白质的三维结构和所产生的功能可能与溶液中的完全不同。界定这些差异是一件具有挑战性的事情。德克萨斯大学奥斯汀分校的劳伦·韦伯博士的研究小组正在利用一个多学科研究项目来应对这些挑战，该项目的重点是研究合理设计和精确准备的表面上的生物分子。韦伯博士鼓励高中生在她自己的实验室里参与研究。特别强调增加德克萨斯州高中的招生努力，以便从事研究的学生的多样性反映出德克萨斯州人口的多样性。尽管生物分子与非生物材料的结合是当前科学关注的一个领域，但对附着在表面的生物分子与溶液中的生物分子的结构和性质之间的差异的了解相对有限。韦伯博士的研究解决了人们对生物分子(如多肽和蛋白质)在这些可选的底物结合环境中发生的变化缺乏基本了解的问题。韦伯博士的实验室正在使用一种独特的化学平台和一套先进的分析工具，从实验和计算的角度来解决这些基本问题。用电子转移蛋白天青对黄金表面进行化学功能化，对该蛋白质功能的研究旨在探索黄金保持稳定的条件。这项研究阐明了表面结合的链肽成核和形成纤维的机制。它还检查了名义上干燥的表面结合蛋白的水化对蛋白质结构和功能的影响。实验结果被用于开发、测试和验证计算方法，这些方法可以准确地预测附着在人造表面上的蛋白质和多肽的结构。韦伯博士的长期目标是促进对多肽和蛋白质在表面行为的化学理解，使理解达到与目前溶液阶段系统可能达到的类似的准确性和可预测性。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Structural Evaluation of Protein/Metal Complexes via Native Electrospray Ultraviolet Photodissociation Mass Spectrometry

• DOI: 10.1021/jasms.0c00066
• 发表时间: 2020-05-06
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Crittenden, Christopher M.;Novelli, Elisa T.;Brodbelt, Jennifer S.
• 通讯作者: Brodbelt, Jennifer S.

Cross-Seeding Controls Aβ Fibril Populations and Resulting Functions

• DOI: 10.1021/acs.jpcb.1c09995
• 发表时间: 2022-03-24
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Lucas, Michael J.;Pan, Henry S.;Webb, Lauren J.
• 通讯作者: Webb, Lauren J.

Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid-β Fibrils

功能化介孔二氧化硅淀粉样蛋白-β原纤维的直接结构多态性

• DOI: 10.1021/acs.langmuir.0c00827
• 发表时间: 2020
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Lucas, Michael J.;Pan, Henry S.;Verbeke, Eric J.;Webb, Lauren J.;Taylor, David W.;Keitz, Benjamin K.
• 通讯作者: Keitz, Benjamin K.

Monitoring damage of self-assembled monolayers using metastable excited helium atoms

使用亚稳态激发氦原子监测自组装单分子层的损伤

• DOI: 10.1063/5.0036827
• 发表时间: 2021
• 期刊: The Journal of Chemical Physics
• 作者: Stratis, Georgios;Zesch, Jordan D.;Pan, Henry S.;Webb, Lauren J.;Raizen, Mark G.
• 通讯作者: Raizen, Mark G.

Characterizing protein–surface and protein–nanoparticle conjugates: Activity, binding, and structure

表征蛋白质-表面和蛋白质-纳米颗粒缀合物：活性、结合和结构

• DOI: 10.1063/5.0101406
• 发表时间: 2022
• 期刊: The Journal of Chemical Physics
• 作者: Correira, Joshua M.;Handali, Paul R.;Webb, Lauren J.
• 通讯作者: Webb, Lauren J.