CAREER: Nucleic Acid-Peptide-Mineral Hybrid Assemblies and Nano-Devices

各种尺度的生命可以被看作是一个动态的自我组装系统。生物体已经发展出独特的策略来构建软组织和硬组织，由此产生的杂交材料具有远远超出人造材料的优异性能。设计自然启发的自组装分子系统和功能材料，可以与细胞通信并调节生物事件，是与合成生物学，纳米技术，再生医学和材料科学等科学领域高度相关的宏伟目标之一。该项目旨在开发自组装核酸-肽-矿物质（NAPM）混合分子瓦作为构建模块，以创建强大的，可编程的，智能的和功能性的生物材料和纳米器件。DNA独特的结构可编程性将与矿物质，肽和RNA的有利机械性能和功能相结合，以多样化和增强DNA纳米结构的化学和物理功能。这个新平台将DNA纳米技术中的可编程组装从纳米级扩展到微米级，提供关于新型混合瓷砖自组装的知识，并导致发现与这些混合系统相关的新功能。此外，该项目将研究与研究生和本科生教育相结合，并为高中，K-12学生和社区范围内的推广引入创新计划。技术总结该项目的总体目标是开发一种混合分子瓦系统，采用矿物质和肽，将其整合到可编程DNA纳米结构中，以产生新的自组装混合材料。需要解决的主要科学挑战是：（1）如何开发一种通用方法来硬化DNA纳米结构，同时保持DNA的可编程性，（2）如何为不同类型矿物的可控精确沉积创造表面偏好，（3）这些新的混合瓦片的自组装行为以及如何引导它们的组装以创建微米级的新颖结构，（4）如何在新系统中实现动态响应重构。在该项目中，这些挑战将通过开发利用调节肽和RNA分子的矿物结构强化沉积方法来解决，以产生NAPM混合瓦片;开发混合瓦片的几何匹配和分子编程规则以指导其自组装;以及通过整合可转换的核酸结构来可逆地改变核酸的大小，形状，和响应外部刺激的杂化材料的表面化学。该项目最终将创建继承DNA和RNA可编程性的混合材料，同时显示增强的机械性能。该奖项反映了NSF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。

NON-TECHNICAL SUMMARYLife at various scales can be viewed as a dynamic self-assembling system. Living organisms have developed their unique strategies to build soft and hard tissues and the resulting hybrid materials have excellent properties that remain far beyond those of their artificial counterparts. To engineer nature-inspired self-assembled molecular systems and functional materials, which can communicate with cells and regulate biological events, is one of the grand goals that is highly relevant to scientific areas ranging from synthetic biology, nanotechnology, regenerative medicine, to materials science. This project aims to develop self-assembling Nucleic Acid-Peptide-Mineral (NAPM) hybrid molecular tiles as building blocks to create robust, programmable, smart, and functional biomaterials and nanodevices. The unique structural programmability of DNA will be integrated with the advantageous mechanical properties and functionality of minerals, peptides, and RNA to diversify and enhance the chemical and physical functionality of DNA nanostructures. This new platform will expand the programmable assembly in DNA nanotechnology from the nanometer scale to microns, furnish knowledge on the self-assembly of novel hybrid tiles, and lead to the discovery of new functionalities associated with these hybrid systems. In addition, this project integrates research with graduate and undergraduate education and introduces innovative programs for high schools, K-12 students, and community-wide outreach.TECHNICAL SUMMARYThe overarching goal of this project is to develop a hybrid molecular tile system employing minerals and peptides that are integrated into programmable DNA nanostructures to generate new self-assembling hybrid materials. The main scientific challenges to address are: (1) how to develop a general method to rigidify DNA nanostructures while maintaining the programmability of DNA, (2) how to create the surface preference for controllable precise deposition of different types of minerals, (3) what are the self-assembly behaviors of these new hybrid tiles and how to guide their assembly to create novel structures at micron scales, and (4) how to achieve dynamic responsive reconfiguration in this new system. In this project, these challenges will be tackled by developing structurally strengthening deposition methods of minerals employing regulating peptides and RNA molecules to produce NAPM hybrid tiles; developing geometric matching and molecular programming rules for the hybrid tiles to direct their self-assembly; and engineering novel reconfiguration mechanisms by integrating switchable nucleic acid structures to reversibly change the size, shape, and surface chemistry of the hybrid materials responding to external stimuli. This project will finally create hybrid materials that inherit the programmability of DNA and RNA while displaying enhanced mechanical properties. It will also develop a toolkit for integrating the physicochemical and mechanical properties of inorganic materials with biological materials.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.