Collaborative Research: Supramolecular Materials by Nucleic Acid Block Copolymer Self-Assembly

非技术性：这些由杜克大学(LEAD)和北卡罗来纳州立大学(NONOL)材料研究部的生物材料计划颁发的协作奖是由化学、生物工程、环境和运输系统部(ENG)的生物医学工程计划共同资助的。这些奖项是为了表彰长DNA链的酶合成以及探索将其组装成聚集体(胶束)和网络的系统科学方法，并有望推动DNA材料领域的发展。这项拟议的研究具有变革性，因为它将为合成多功能DNA链提供设计规则，这些链可以自组装成具有药物输送应用潜力的形态。这项拟议的研究还将产生在大范围内制造定向DNA纳米线网络的方法和策略。这些多核苷酸网络可以金属化，从而有助于快速增长的纳米设备数量的基本需求，其应用范围从柔性电子到光伏。拟议的项目也是名为反向工程生物学(REBio)的研究和培训范式的象征，在该范式中，学生将把生物科学整合到设计的工程范式中，以向前设计新的产品和过程。在REBio范式下，私人投资机构致力于：(I)为参与该项目的本科生和研究生提供综合教育和研究培训计划；以及(Ii)通过为K-12学生和普通受众提供实践和非正式教育机会，提高公众对拟议研究背后的一些科学概念的认识和参与。技术：聚电解质嵌段共聚聚合物在溶液中显示出丰富的胶束化行为，并有望在纳米和生物技术应用中应用于新型功能材料。然而，到目前为止，合成高分子量的多核苷酸和寡核苷酸杂化嵌段共聚物仍然是一个挑战。此外，对嵌段共聚多核苷酸形成的胶束形态的设计规则知之甚少。尽管在DNA纳米技术领域取得了惊人的成功，但表面多核苷酸组装的排列、图案化和大规模有序仍然是阻碍这些材料在功能器件中使用的挑战性问题。这一跨学科、协作研究提案中的研究活动解决了这些不足。研究小组将结合理论、实验和模拟回答三个具体目标的问题：(1)为在水溶液中合成和自组装成一系列胶束结构的嵌段共聚多核苷酸提供指南；(2)对表面上功能核酸网络的组装以及将这些网络用作金属化支架的基础了解和控制；以及(3)提供成本效益高的末端脱氧核苷酸转移酶，这是多核苷酸材料合成放大所需的。

Nontechnical: These Collaborative awards by the Biomaterials program in the Division of Materials Research to Duke University (Lead) and North Carolina State University (Nonlead) are cofunded by the Biomedical Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems (ENG). These awards are for the enzymatic synthesis of long DNA chains and the systematic scientific approaches for exploring their assembly into aggregates (micelles) and networks, and are expected to advance the field of DNA-based materials. The proposed research is transformative because it will provide design rules for the synthesis of multi-functional DNA chains that can self-assemble into morphologies with potential for drug delivery applications. The proposed research will also yield methods and strategies to fabricate oriented DNA nanowire networks over large areas. These polynucleotide networks can be metallized and thus contribute to an essential need in the rapidly growing number of nanoscale devices with applications ranging from flexible electronics to photovoltaics. The proposed projects are also emblematic for a research and training paradigm termed Reverse Engineering Biology (REBio), where students will integrate biological sciences within the engineering paradigm of design to forward engineer new products and processes. Under the REBio paradigm, the PIs are committed to: (i) providing an integrated educational and research training program for undergraduate and graduate students involved with the project; and (ii) increasing public awareness and engagement with some of the scientific concepts underlying the proposed research through hands-on, informal education opportunities for K-12 students and general audiences.Technical: Polyelectrolyte block-co-polymers show rich micellization behavior in solution and hold promise for novel functional materials in nano- and biotechnological applications. To date, however, the synthesis of polynucleotides with high molecular weight, and of oligonucleotide hybrid block-copolymers is still a challenge. Moreover, little is known about the design rules for micellar morphologies formed by block-co-polynucleotides. Despite the astounding successes in the field of DNA nanotechnology, the alignment, patterning and large scale ordering of polynucleotide assemblies on surfaces are still challenging problems that prevent use of these materials in functional devices. The research activities in this interdisciplinary, collaborative research proposal address these shortcomings. The research team will combine theory, experiment and simulations to answer questions in three specific aims: (1) to provide guidelines for synthesis and self-assembly of block-co-polynucleotides into a range of micellar structures in aqueous solutions; (2) to develop fundamental understanding and control over the assembly of functional nucleic acid networks on surfaces and the use of the networks as scaffolds for metallization; and (3) to provide cost-effective access to terminal deoxynucleotidyl Transferase needed for the scale-up of polynucleotide materials synthesis.