CAREER: Programmable Peptide Nucleic Acid Molecules as Building-blocks for Complex Nanostructures

职业：可编程肽核酸分子作为复杂纳米结构的构建模块

• 批准号: 1944130
• 负责人: Rebecca Taylor
• 金额: $ 52.5万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1944130&HistoricalAwards=false
• 关键词: CAREER; Programmable; Peptide; Nucleic; Acid

This Faculty Early Career Development (CAREER) grant supports fundamental studies of the thermodynamic stability, morphology, and mechanics of a new type of nucleic acid nanotechnology built using a synthetic mimic of deoxyribonucleic acid or DNA. The programmability and responsive nature of nucleic acid-based nanostructures, nanomaterials and nanomachines give them the potential to transform nanosensing as well as manufacturing from the nanoscale to the mesoscale. However, without protection, DNA-based nanosystems can be unstable in organic solvents commonly used in polymer and peptide synthesis. This award investigates the processing-formation-mechanics relationships in novel, programmable gamma peptide nucleic acid (gammaPNA)-based materials for use in nanomanufacturing processes that depend on aggressive organic solvent solutions. This project advances the knowledge of nucleic acid self-assembly in the field of advanced manufacturing and has the potential to enable sequence-specific polymer synthesis as well as novel peptide assembly processes in polar organic solvents. The objective of the integrated education plan is to investigate voice assistants for advanced manufacturing education, research, and industrial workforce development. To this end, voice assistants are used in the classroom and in the laboratory for supportive training and education that demonstrates the importance of NIST and ASTM standards for nanomanufacturing.The specific goal of this research is to discover the design rules for building complex nanostructures with a preorganized synthetic DNA mimic. While preliminary studies suggest that gammaPNA can successfully hybridize in harsh environments and form filamentous nanostructures according to molecular programs defined by Watson-Crick base pairing, the morphology and mechanics of these nanostructures appear to be modulated by the solution conditions as well as the structural assembly motif and the gamma chemical modifications. This research investigates the effect of organic solvent type and concentration on the stability of all gammaPNA nanostructures. Using total internal fluorescence microscopy and transmission electron microscopy (TEM), the project investigates how substitution with DNA affects the thermodynamics of formation and melting of hybrid gammaPNA-DNA nanotube structures. Using TEM, the nanoscale morphology and “weave structure” are characterized, and, using persistence length studies, bending stiffness as a function of solvent and proportion of DNA is determined. Finally, the use of micropatterned seed features for templated growth and surface coating with these gammaPNA nanomaterials is investigated. Unlike electronegative DNA-based systems, PNA-based systems have a tendency to stick together forming bundles. By leveraging that distinct characteristic, superstructure formation using not only gammaPNA oligomer sequence but also external conditions like surface hydrophobicity could be controlled.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.

这项教师早期职业发展（Career）基金支持对一种新型核酸纳米技术的热力学稳定性、形态和力学的基础研究，这种纳米技术使用脱氧核糖核酸或DNA的合成模拟物来构建。基于核酸的纳米结构、纳米材料和纳米机器的可编程性和响应性赋予了它们将纳米传感和制造从纳米尺度转变为中尺度的潜力。然而，如果没有保护，基于dna的纳米系统在聚合物和肽合成中常用的有机溶剂中可能不稳定。该奖项研究了新型可编程γ肽核酸（gammaPNA）材料的加工-形成-力学关系，这些材料用于依赖于侵略性有机溶剂溶液的纳米制造过程。该项目在先进制造领域推进了核酸自组装的知识，并有可能在极性有机溶剂中实现序列特异性聚合物合成以及新型肽组装工艺。综合教育计划的目的是研究语音辅助技术在先进制造业教育、研究、产业人力培养等方面的应用。为此，语音助手在教室和实验室中用于支持性培训和教育，这表明了NIST和ASTM标准对纳米制造的重要性。本研究的具体目标是发现用预先组织的合成DNA模拟物构建复杂纳米结构的设计规则。虽然初步研究表明，gammaPNA可以在恶劣环境中成功杂交，并根据沃森-克里克碱基配对定义的分子程序形成丝状纳米结构，但这些纳米结构的形态和力学似乎受到溶液条件以及结构组装基序和γ化学修饰的调节。本研究考察了有机溶剂类型和浓度对所有γ mapna纳米结构稳定性的影响。利用全内部荧光显微镜和透射电子显微镜（TEM），该项目研究了DNA取代如何影响杂化gammaPNA-DNA纳米管结构的形成和熔化热力学。利用透射电镜，表征了纳米尺度的形态和“编织结构”，并通过持续长度研究，确定了弯曲刚度作为溶剂和DNA比例的函数。最后，研究了使用微图案种子特征进行模板化生长和表面涂覆这些γ mapna纳米材料。与电负性的dna系统不同，pna系统倾向于粘在一起形成束。通过利用这一独特的特性，不仅可以利用gammaPNA寡聚物序列形成上层结构，还可以控制表面疏水性等外部条件。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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

Modular self-assembly of gamma-modified peptide nucleic acids in organic solvent mixtures

有机溶剂混合物中伽马修饰肽核酸的模块化自组装

• DOI: 10.1038/s41467-020-16759-8
• 发表时间: 2020
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Kumar, Sriram;Pearse, Alexander;Liu, Ying;Taylor, Rebecca E.
• 通讯作者: Taylor, Rebecca E.

Self-Assembly of Gamma-Modified Peptide Nucleic Acids into Complex Nanostructures in Organic Solvent Mixtures

γ-修饰肽核酸在有机溶剂混合物中自组装成复杂纳米结构

• DOI: 10.3791/61351
• 发表时间: 2020
• 期刊: Journal of Visualized Experiments
• 作者: Kumar, Sriram;Liu, Ying;Taylor, Rebecca E.
• 通讯作者: Taylor, Rebecca E.

Modular, Articulated Models of DNA and Peptide Nucleic Acids for Nanotechnology Education

用于纳米技术教育的 DNA 和肽核酸的模块化、铰接模型

• DOI: 10.35459/tbp.2022.000225
• 发表时间: 2023
• 期刊: The Biophysicist
• 作者: Goodwin-Schoen, Caleigh M.;Taylor, Rebecca E.
• 通讯作者: Taylor, Rebecca E.

Rapid self‐assembly of γPNA nanofibers at constant temperature

γPNA 纳米纤维在恒温下快速自组装

• DOI: 10.1002/bip.23463
• 发表时间: 2021
• 期刊: Biopolymers
• 影响因子: 2.9
• 作者: Kumar, Sriram;Dhami, Isha;Thadke, Shivaji A.;Ly, Danith H.;Taylor, Rebecca E.
• 通讯作者: Taylor, Rebecca E.