Bilingual Biopolymers: Harnessing Dual Information Codes to Control Assembly

非技术性：该奖项由埃默里大学材料研究部的生物材料项目授予，旨在探索可用于药物和毒素检测或治疗药物控制输送的新型仿生材料。核酸和蛋白质都具有编码信息和执行特定功能的能力，但它们各自受益于关于功能的可设计性和广度的独特优势。到目前为止，所有试图模仿这些天然生物聚合物的聚合物都只利用了一个单一的密码--核酸或蛋白质。这项工作探索了能够同时编码核酸和蛋白质信息的新型聚合物，从而对结构和功能提供更大的控制。具体来说，该研究将探索这些聚合物组装体进入细胞的吸收以及它们结合和释放小分子（如治疗剂）的能力。此外，该提案还将探索模仿自然界中发现的控制结构的新模式。该研究项目将跨越材料科学，化学和分子生物学领域，为本科生和研究生提供涉及使用尖端技术的高度跨学科培训经验。该项目还将通过在PI教授的课程中实施的科学传播项目，以及通过PI作为高中国际科学博览会的评委和学生导师的参与，为公众的科学素养做出贡献。美国国家科学基金会这项提案的首要研究目标是探索“双语生物聚合物”作为一类新的可编程材料，其能够解释肽和核酸信息代码以指导组装、拆卸和客体释放。肽核酸（PNA）作为这些聚合物的理想支架，因为它具有可以用氨基酸侧链官能化的肽样骨架，并且能够序列特异性地结合DNA和RNA。利用先前的NSF支持，该团队生成并表征了具有两亲性氨基酸代码的“双语”PNA序列，以驱动组装成胶束。他们证明了在互补DNA或RNA序列存在下的刺激响应性分解，以及细胞渗透性和螯合疏水客体分子的能力。基于这些令人兴奋的结果，拟议的实验旨在：（1）评估侧链结构和模式对组装和小分子结合能力的影响;（2）研究胶束大小和表面性质对细胞摄取和小分子释放的影响;（3）通过化学可寻址交联扩大刺激响应控制组装的范围。拟议研究的更广泛影响包括旨在改善本科生教育和公众科学素养的活动，以及通过开发改进的诊断和药物输送平台造福公众健康的潜力。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: This award by the Biomaterials program in the Division of Materials Research to Emory University is for exploration of new biomimetic materials that can be used for applications in the detection of drugs and toxins, or for the controlled delivery of therapeutics. Both nucleic acids and proteins have the ability to encode information and perform specific functions, yet they each benefit from unique advantages with regard to designability and breadth of function. To date, all polymers seeking to mimic these natural biopolymers only take advantage of a single code – either nucleic acid or protein. The proposed work explores novel polymers that are able to simultaneously encode both nucleic acid and protein information, in turn providing greater control over structure and function. Specifically, the research will explore the uptake of these polymer assemblies into cells and their ability to bind and release small molecules such as therapeutics. Additionally, the proposal will explore new modes for controlling structure that mimic those found in nature. This research project will span the fields of materials science, chemistry, and molecular biology, providing undergraduate and graduate students with a highly interdisciplinary training experience involving the use of cutting-edge techniques. This project will also contribute to public scientific literacy through a science communication project implemented in a course taught by the PI, as well as through the PI’s participation as a judge and student mentor for the high school International Science Fair.Technical: The overarching research goal of this NSF proposal is to explore “bilingual biopolymers” as a new class of programmable materials capable of interpreting both peptide and nucleic acid information codes to direct assembly, disassembly, and guest release. Peptide nucleic acid (PNA) serves as an ideal scaffold for these polymers, as it has a peptide-like backbone that can be functionalized with amino acid side chains, and is able to bind sequence-specifically to DNA and RNA. Using prior NSF support, this team generated and characterized “bilingual” PNA sequences having an amphiphilic amino acid code to drive assembly into micelles. They demonstrated stimuli-responsive disassembly in the presence of a complementary DNA or RNA sequence, as well as cell permeability and the ability to sequester hydrophobic guest molecules. Building upon these exciting results, the proposed experiments aim to: (1) Evaluate the effect of side chain structure and pattern on assembly and small-molecule binding capabilities; (2) Investigate the effect of micelle size and surface properties on cellular uptake and small-molecule release; (3) Expand the scope of stimuli-responsive control of assembly via chemically addressable cross-links. The broader impacts of the proposed research include activities aimed at improving undergraduate education and public scientific literacy, and the potential to benefit public health through the development of improved diagnostics and drug delivery platforms.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.