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

这项学院早期职业发展(Career)补助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，这种纳米技术是使用合成的脱氧核糖核酸或DNA的模拟物构建的。基于核酸的纳米结构、纳米材料和纳米机械的可编程性和响应性使它们有可能将纳米传感和制造从纳米尺度转变为介观尺度。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伽马多肽核酸(GammaPNA)材料的加工-形成-力学关系，这些材料用于依赖侵略性有机溶剂溶液的纳米制造工艺。该项目推进了先进制造领域的核酸自组装知识，并有可能实现序列特定的聚合物合成以及在极性有机溶剂中的新肽组装工艺。综合教育计划的目标是研究用于先进制造业教育、研究和工业劳动力发展的语音助手。为此，语音助手被用于教室和实验室的支持性培训和教育，以证明NIST和ASTM标准对纳米制造的重要性。这项研究的具体目标是发现利用预先组织的合成DNA模拟物来构建复杂纳米结构的设计规则。虽然初步研究表明，根据Watson-Crick碱基配对定义的分子程序，GammaPNA可以在恶劣的环境中成功杂交并形成丝状纳米结构，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伽马化学修饰的调制。本研究考察了有机溶剂的种类和浓度对所有γ-PNA纳米结构稳定性的影响。利用全内荧光显微镜和透射电子显微镜，该项目研究了DNA取代如何影响杂化伽马PNA-DNA纳米管结构的形成和熔化的热力学。利用透射电子显微镜对纳米级的形貌和“编织结构”进行了表征，并利用持续时间研究，确定了弯曲刚度与溶剂和DNA比例的关系。最后，研究了微图案化种子特征在模板生长和表面包覆这些伽马PNA纳米材料中的应用。与基于DNA的电阴性系统不同，基于PNA的系统有一种粘连在一起形成束的趋势。通过利用这一独特的特征，不仅可以控制使用GammaPNA低聚物序列的超结构形成，还可以控制外部条件，如表面疏水性。该奖项反映了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。

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.