Collaborative Research: Exploring self-organization of functional nucleic acid supramolecular assemblies with stimuli responsive properties

该项目由生物材料计划和刺激竞争研究的既定计划（EPSCoR）第1部分：非技术总结共同资助核糖核酸或RNA的研究对于了解生命所需的主要细胞过程以及各种疾病的起源至关重要。通过使用合理设计的RNA作为构建模块，可以组装具有预定义性质和结构的核酸纳米颗粒或NANP。容易响应生物环境变化的能力使得生物相容性NANP成为临床应用的有吸引力的材料。此外，NANP的生物化学多功能性可以与无机纳米材料的光学，电子和磁性相结合。然后，这些增强的NANP可以被组织成具有受控复杂性和功能的超分子组装体，适用于广泛的生物医学、电子和成像应用。然而，尽管最近的进展，它仍然是一个挑战，工程复杂的，响应性，NANP超组装与规范的形态。拟议的研究计划旨在开发一个可推广的工具包，用于构建为生物技术最终用户设计的基于刺激响应NANP的材料。构建功能性NANP超组装体将改善当前治疗系统的性能，允许可重构生物材料的工程化，并有助于进一步理解控制内源性生物分子功能的相互作用。在此期间，本科生和研究生将接受实验和计算RNA纳米技术的多学科培训。该项目还将扩大名为ouRNAno的教育领域，向社区宣传RNA纳米技术领域的最新进展，并将继续通过与当地学校和科学博物馆举办社区STEM活动来培养研究的热情。第二部分：RNA纳米技术受益于RNA通过形成12个几何家族的规范和非规范碱基配对组装的能力。这提供了一组不同的结构和相互作用的基序，其允许构建核酸纳米颗粒（NANP）。NANP的多功能生物化学可以与无机纳米材料的光学，电子和磁性相结合。将这些增强的NANP进一步组织成具有受控结构复杂性的合理设计的超分子组装体，可以用于生物光学、响应装置的设计、软仿生机器、组织模拟物和人造肌肉中的应用。尽管存在NANP设计的计算工具，但使用NANP作为超分子组装的模块化构建块从未被系统地研究过。因此，该研究计划旨在通过开发一种可推广的基于NANP的可编程平台来解决这一知识差距，该平台通过独立可编程的结构参数网络同时编码目标理化，机械和生物特性。为了实现这些目标，该团队提出了三个主要目标：（i）将NANP的可编程参数与其超分子组装体的物理化学和机械性能相关联;（ii）评估无机纳米材料对单个NANP的功能化对其超分子组装体的物理化学和机械性能的影响;和（iii）研究刺激依赖的动力学途径对功能性超分子组装体性质的影响。该项目将大大推进NANP超组件作为新型刺激响应材料的工程框架，并使其能够在生物医学，电子和成像应用中广泛使用。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project is jointly funded by the Biomaterials program and the Established Program to Stimulate Competitive Research (EPSCoR)PART 1: NON-TECHNICAL SUMMARYThe study of ribonucleic acid or RNA is essential for understanding major cellular processes needed for life as well as the origin of various diseases. By using rationally designed RNAs as building blocks, it becomes possible to assemble Nucleic Acid NanoParticles, or NANPs, with pre-defined properties and architectures. The ability to readily respond to changes in biological environments makes biocompatible NANPs an attractive material for clinical use. Also, the biochemical versatility of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. These augmented NANPs can then be organized into supramolecular assemblies with controlled complexity and functions suitable for a broad range of biomedical, electronic, and imaging applications. However, despite the recent progress, it is still a challenge to engineer sophisticated, responsive, NANP supra-assemblies with regulated morphology. The proposed research program aims to develop a generalizable toolkit for the construction of stimuli-responsive NANP-based materials designed for end users in biotechnology. Building functional NANP supra-assemblies will improve the performance of current therapeutic systems, allow for the engineering of reconfigurable biomaterials, and become instrumental in furthering our understanding of the interactions governing the function of endogenous biomolecules. During this program, the undergraduate and graduate students will receive multidisciplinary training in experimental and computational RNA nanotechnology. This project will also expand the educational domain called ouRNAno that reaches out to and informs the community about recent advances in the field of RNA nanotechnology and will continue cultivating excitement for research through hosting community STEM events with local schools and science museum. PART 2: TECHNICAL SUMMARYRNA nanotechnology benefits from RNA’s ability to assemble through both canonical and non-canonical base pairings that form 12 geometric families. This offers a diverse set of structural and interacting motifs which allow for the construction of Nucleic Acid NanoParticles (NANPs). The versatile biochemistry of NANPs can be combined with the optical, electronic, and magnetic properties of inorganic nanomaterials. The further organization of these augmented NANPs into rationally designed supramolecular assemblies with controlled structural complexity can be used for application in biooptics, design of responsive devices, soft biomimetic machines, tissue mimics, and artificial muscles. Despite the existence of computational tools for NANP design, the use of NANPs as modular building blocks for supramolecular assemblies has never been systematically investigated. Therefore, this research program aims to address this gap in knowledge by developing a generalizable NANP-based programmable platform that simultaneously encodes targeted physicochemical, mechanical, and biological properties through networks of independently programmable architectural parameters. To achieve these goals, the team proposes three main objectives: (i) correlate the programmable parameters of NANPs with the physicochemical and mechanical properties of their supramolecular assemblies; (ii) evaluate the effect of functionalization of individual NANPs with inorganic nanomaterials on the physicochemical and mechanical properties of their supramolecular assemblies; and (iii) investigate the effect of stimuli-dependent kinetic pathways on the properties of functional supramolecular assemblies. This project will substantially advance the framework for the engineering of NANP supra-assemblies as novel stimuli-responsive materials and enable their use in a broad range of biomedical, electronic, and imaging applications.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.