Functional DNA Nanostructures

功能性 DNA 纳米结构

• 批准号: 1827346
• 负责人: Aleksei Aksimentiev
• 金额: $ 35.53万
• 依托单位: University of Illinois at Urbana-Champaign
• 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: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1827346&HistoricalAwards=false
• 关键词: Functional; DNA; Nanostructures

NONTECHNICAL SUMMARYThis award supports theoretical and computational research and education on exploiting DNA self-assembly to develop a new class of functional materials that outperform their analogs in biological systems. Development of man-made systems that reproduce the functionality and outperform biological systems is one of the most challenging and intriguing aims of science and engineering. Miniature systems that perform practical tasks are in demand in all areas of modern technology, from protective clothing, filtration, and electronics to synthetic enzymes and artificial tissues. Self-assembly of DNA molecules programmed by the letters of the genetic alphabet has emerged as a practical method for building complex miniature objects. Driven by the complementary pairing of A and T and C and G DNA bases, such molecular self-assembly is robust and occurs in a massively parallel fashion. Using an arsenal of computational approaches, this project will develop man-made DNA systems capable of performing the functions of naturally occurring biological machines, including ones that alter the composition of biological membranes, use electricity to power rotary motors, harness the energy of light to generate thrust, and remain functional in the cellular environment. Products of the research will be used to educate the next generation of scientists and engineers through new graduate and undergraduate courses, annual hands-on workshops, interactive demonstrations of scientific concepts and lessons for middle school and high school students. Ultimately, this project will contribute to the development of synthetic systems capable of performing diverse functions of biological systems without the complexities required to sustain biological life.TECHNICAL SUMMARYThis award supports theoretical and computational research and education to investigate self-assembly of DNA as a way to develop a new class of functional nanostructures that reproduce and exceed the functionality of biological systems. All-atom, coarse-grained and continuum models of nanoscale interactions will be combined to obtain an accurate description of the electrostatic, optical, hydrodynamic and thermodynamic forces that give rise to the nanostructures with desired functionalities. The PI will focus on DNA nanostructures that can be inserted into lipid membranes in response to external stimuli to regulate the passage of nutrients and signals across cellular boundaries and to alter the composition of the biological membranes. DNA systems will be designed to convert light or an electric field into forces and torques to power nanoscale rotary motors and artificial muscles. The PI aims to elucidate the properties of self-assembled DNA systems in the crowded environment of a biological cell and to devise new methods to keep the DNA nanostructures functional in such an environment. New computational approaches for engineering matter at the nanoscale, enabling theoretical studies of systems that combine unfamiliar combinations of materials and physical interactions, will be developed in the course of the research. The research will advance understanding of the physics of assemblies that combine highly charged and hydrophobic objects, liquid flow in complex nanoscale structures, the effects of highly focused light on self-assembled DNA structures and the behavior of man-made systems inside biological cells. The methodological advances enabled through this project will be disseminated to the research community in the form of modules for well-used community software packages, including VMD, NAMD and ARBD; through self-study materials; and an annual hands-on workshop focused on modeling self-assembled nanostructures. The project outcomes will be integrated into graduate and undergraduate curricula in the form of topical modules that introduce microscopic simulations as a design and discovery tool and self-assembly as a new engineering paradigm. The project will engage K-12 students and their families through interactive demonstrations of scientific concepts and integration of research products into middle and high-school curricula.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.

非技术摘要该奖项支持利用 DNA 自组装来开发一类新型功能材料的理论和计算研究以及教育，这些材料在生物系统中的性能优于其类似物。开发能够重现功能并超越生物系统的人造系统是科学和工程中最具挑战性和最有趣的目标之一。从防护服、过滤和电子产品到合成酶和人造组织，现代技术的所有领域都需要执行实际任务的微型系统。由遗传字母表中的字母编程的 DNA 分子的自组装已成为构建复杂微型物体的实用方法。在 A 和 T 以及 C 和 G DNA 碱基互补配对的驱动下，这种分子自组装是稳健的，并且以大规模并行的方式发生。该项目将使用一系列计算方法，开发能够执行自然生物机器功能的人造 DNA 系统，包括改变生物膜的组成、使用电力为旋转电机提供动力、利用光能来实现生物机器的功能。产生推力，并在细胞环境中保持功能。该研究的产品将用于通过新的研究生和本科生课程、年度实践研讨会、科学概念的互动演示以及中学生和高中生的课程来教育下一代科学家和工程师。最终，该项目将有助于开发能够执行生物系统多种功能的合成系统，而无需维持生物生命所需的复杂性。技术摘要该奖项支持理论和计算研究及教育，以研究 DNA 自组装作为一种方法开发一类新型功能纳米结构，可复制并超越生物系统的功能。 纳米级相互作用的全原子、粗粒和连续模型将被结合起来，以获得对静电、光学、流体动力和热力学力的准确描述，从而产生具有所需功能的纳米结构。该 PI 将重点研究 DNA 纳米结构，这种结构可以插入脂质膜中，以响应外部刺激，调节营养物质和信号穿过细胞边界的通道，并改变生物膜的组成。 DNA 系统将被设计为将光或电场转化为力和扭矩，为纳米级旋转电机和人造肌肉提供动力。该 PI 旨在阐明生物细胞拥挤环境中自组装 DNA 系统的特性，并设计新方法以保持 DNA 纳米结构在这种环境中发挥功能。 研究过程中将开发纳米级工程物质的新计算方法，从而能够对结合了不熟悉的材料组合和物理相互作用的系统进行理论研究。该研究将加深对结合高电荷和疏水物体的组装体物理、复杂纳米级结构中的液体流动、高度聚焦光对自组装 DNA 结构的影响以及生物细胞内人造系统行为的理解。通过该项目实现的方法学进步将以常用社区软件包模块的形式传播给研究社区，包括 VMD、NAMD 和 ARBD；通过自学材料；以及一年一度的实践研讨会，重点是自组装纳米结构的建模。该项目成果将以主题模块的形式纳入研究生和本科生课程，引入微观模拟作为设计和发现工具，并将自组装作为新的工程范例。该项目将通过科学概念的互动演示以及将研究产品融入初中和高中课程，吸引 K-12 学生及其家庭。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进行评估，被认为值得支持以及更广泛的影响审查标准。

项目成果

Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures

阳离子调节 DNA 纳米结构的膜附着和功能

• DOI: 10.1021/jacs.1c00166
• 发表时间: 2021-05
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Morzy, Diana;Rubio;Joshi, Himanshu;Aksimentiev, Aleksei;Di Michele, Lorenzo;Keyser, Ulrich F.
• 通讯作者: Keyser, Ulrich F.

Dynamic Interactions between Lipid-Tethered DNA and Phospholipid Membranes

脂质束缚 DNA 和磷脂膜之间的动态相互作用

• DOI: 10.1021/acs.langmuir.8b02271
• 发表时间: 2018-10
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Arnott, Patrick M.;Joshi, Himanshu;Aksimentiev, Aleksei;Howorka, Stefan
• 通讯作者: Howorka, Stefan

DNA Origami Voltage Sensors for Transmembrane Potentials with Single-Molecule Sensitivity

用于单分子灵敏度跨膜电位的 DNA 折纸电压传感器

• DOI: 10.1021/acs.nanolett.1c02584
• 发表时间: 2021-10
• 期刊: Nano Letters
• 影响因子: 10.8
• 作者: Ochmann, Sarah E.;Joshi, Himanshu;Büber, Ece;Franquelim, Henri G.;Stegemann, Pierre;Saccà, Barbara;Keyser, Ulrich F.;Aksimentiev, Aleksei;Tinnefeld, Philip
• 通讯作者: Tinnefeld, Philip

Rosette Nanotube Porins as Ion Selective Transporters and Single-Molecule Sensors

作为离子选择性转运蛋白和单分子传感器的玫瑰花结纳米管孔蛋白

• DOI: 10.1021/jacs.9b10993
• 发表时间: 2019-12
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Tripathi, Prabhat;Shuai, Liang;Joshi, Himanshu;Yamazaki, Hirohito;Fowle, William H.;Aksimentiev, Aleksei;Fenniri, Hicham;Wanunu, Meni
• 通讯作者: Wanunu, Meni

High-Fidelity Capture, Threading, and Infinite-Depth Sequencing of Single DNA Molecules with a Double-Nanopore System

使用双纳米孔系统对单个 DNA 分子进行高保真捕获、穿线和无限深度测序

• DOI: 10.1021/acsnano.0c06191
• 发表时间: 2020-11-24
• 期刊: ACS Nano
• 影响因子: 17.1
• 作者: Choudhary A;Joshi H;Chou HY;Sarthak K;Wilson J;Maffeo C;Aksimentiev A
• 通讯作者: Aksimentiev A