DNA Origami Nanostructures with Complex Curvatures in 3D Space

ID: MPS/DMR/BMAT(7623) 1104373 PI: Yan， Hao ORG：亚利桑那州立大学标题：三维空间中具有复杂曲率的DNA折纸纳米结构知识分子优点：纳米技术和生物材料领域的一个重大挑战是组装任意的三维（3D）纳米结构，并完全控制材料的形状。为了应对这一挑战，PI将开发各种新颖的策略来构建在三维空间中具有复杂曲率的自组装DNA纳米结构。更具体地说，他建议开发一种自组装系统：(1)使用DNA折纸折叠技术产生包含复杂曲率的3D DNA纳米结构。(2)创建一组几何楔形DNA纳米结构，通过靶向插入和删除来指导预先形成的平面DNA纳米结构的曲率。(3)利用弯曲的3D DNA折纸纳米结构作为支架，模拟组蛋白在基因包装中的作用，并为后续研究制造人工核小体。这项新技术将利用与结构DNA纳米技术相关的特殊可寻址性和空间控制来生产类似于存在于生物结构中的构象复杂性的人工结构平台，从而为工程新型生物启发、仿生和生物抑制材料创造前所未有的机会。本提案中包含的设计策略提出了应对这一挑战的基本步骤。该提案旨在实现具有高可编程性和复杂性的3D纳米结构的自组装，并随后将其用作模拟核小体功能的支架。此外，所提出的研究将为基于dna的纳米制造提供各种新的和重要的方法。该项目最终寻求超越当前制造任意形状3D纳米结构的自上而下技术的明显限制。这将导致更小、更快、更多样化的纳米级结构，用于从能源到生物诊断设备的广泛应用。更广泛的影响：这项研究具有广泛的社会意义。随着PIs推进纳米技术的新技术发展，他们的研究为本科生和研究生提供了接受先进科学培训的机会，并为亚利桑那州立大学向社区提供了教育推广。Yan和Liu在亚利桑那州立大学的团队位于生物设计研究所，该研究所特别强调跨学科研究。生物设计研究所提供了一个招收不同背景的学生的机会，包括化学和生物化学、工程、物理和生命科学。少数民族和女学生也被积极招募。此外，每年夏天，生物设计研究所和亚利桑那州立大学还为当地高中生和初中和高中教师提供研究机会[教师暑期研究经验（RET）和高中生暑期实习计划（SIP），以及亚利桑那州科学教师进步和研究培训（AZ-START）]。PI和联合PI积极参与了这些项目，在他们的实验室接待了几位少数民族高中教师和学生。他们预计在每年夏天招募更多的高中生参与拟议的研究，并计划与当地高中化学和科学教师合作设计一个名为DNA纳米实验室的交互式在线课程，旨在向高中生、本科生和公众介绍DNA纳米技术。课程材料将包括文字介绍和实验照片、视频演示和实验过程的动画。这将使许多无法参加竞争激烈的实习项目的学生受益。这项拟议研究的项目也将用于实验室模块，为对纳米技术感兴趣的更大的社区开发基于网络的培训协议。

ID: MPS/DMR/BMAT(7623) 1104373 PI: Yan, Hao ORG: Arizona State UniversityTitle: DNA Origami Nanostructures with Complex Curvatures in 3D SpaceINTELLECTUAL MERIT: A grand challenge in the fields of nanotechnology and biomaterials is to assemble arbitrary, three-dimensional (3D) nanostructures with complete control of the material shape. To address this challenge, the PI will develop various novel strategies to construct self-assembling DNA nanostructures that possess complex curvatures in 3D space. More specifically, he proposes to develop a self-assembling system to: (1) Produce 3D DNA nanostructures that contain intricate, complex curvatures using the DNA origami folding technique. (2) Create a set of geometric, wedge-like DNA nanostructures to direct the curvature of preformed, planar DNA nanostructures using targeted insertion and deletion. (3) Utilize curved, 3D DNA origami nanostructures as scaffolds to mimic the role of histone proteins in gene packaging and create artificial nucleosomes for subsequent study. This new technology will exploit the exceptional addressability and spatial control associated with structural DNA nanotechnology to produce an artificial structural platform that resembles the conformational complexity that exists in biological structures, thus creating unprecedented opportunities for engineering novel bioinspired, biomimetic, and biokleptic materials. The design strategies included in this proposal present fundamental steps toward meeting this challenge. The proposal aims to achieve self-assembly of 3D nanostructures with high programmability and complexity, and subsequently use them as scaffolds to mimic the functionality of nucleosomes. Furthermore, the proposed research will provide various new and significant approaches to DNA-based nanofabrication. This project ultimately seeks to go beyond the evident limits of current top-down techniques for the fabrication of arbitrary shaped 3D nanostructures. This will lead to smaller, faster, and more diverse nanoscale structures for a wide range of applications from energy to bio-diagnostic devices.BROADER IMPACTS: There are broad societal implications for this research. As the PIs advance nanoscale techniques for the development of novel technologies, their research leads to opportunities for undergraduate and graduate student to receive advanced scientific training, and for educational outreach to the community by ASU. Yan and Liu's teams at ASU are located in the Biodesign Institute, which places special emphasis on interdisciplinary research. The Biodesign Institute provides an opportunity to recruit students with various backgrounds including chemistry and biochemistry, engineering, physics, and life science. Also actively recruited are minority and female students. In addition, every summer the Biodesign Institute and ASU also provide research opportunities to local high school students and to middle and high school teachers [Summer Research Experience for Teachers (RET) and High School Student Summer Internship Program (SIP), and Arizona Science Teacher Advancement and Research Training (AZ-START)]. The PI and co-PI have actively participated in these programs, hosting several minority high school teachers and students in their labs. They anticipate the recruitment of additional high school students to participate in the proposed research during each summer and plan to collaborate with local high school chemistry and science teachers to design an interactive online course called DNA Nano Laboratory, aiming to introduce DNA nanotechnology to high school students, undergraduate students and the public. Course materials will include text introductions and laboratory photographs, video demonstrations, and animations of experimental procedures. This will benefit a multitude of students who are not able to participate in the highly competitive internship programs. Projects from this proposed research will also be used in laboratory modules for the development of a web-based training protocol for a larger community interested in nanotechnology.