Bilingual Biopolymers: Harnessing Dual Information Codes to Control Assembly

双语生物聚合物：利用双信息代码来控制组装

• 批准号: 2313695
• 负责人: Jennifer Heemstra
• 金额: $ 42.86万
• 依托单位: Washington University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2313695&HistoricalAwards=false
• 关键词: Bilingual; Biopolymers; Harnessing; Dual; Information

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.

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，表彰可用于药物和毒素检测或治疗药物受控输送的新型仿生材料的探索。核酸和蛋白质都有编码信息和执行特定功能的能力，但它们各自都受益于在可设计性和功能广度方面的独特优势。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单一的密码--要么是核酸，要么是蛋白质。这项拟议的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，进而提供了对结构和功能的更好控制。具体地说，这项研究将探索这些聚合物组件进入细胞的吸收情况，以及它们结合和释放小分子(如治疗药物)的能力。此外，该提案将探索模仿自然界中发现的结构的控制结构的新模式。这项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的培训经验。这个项目还将通过由国际科学协会教授的一门课程中实施的科学交流项目，以及通过国际科学协会作为评委和高中国际科学博览会的学生导师的参与，来促进公众的科学素养。技术：这项NSF提案的总体研究目标是探索作为一种新的能够解释肽和核酸信息编码的可编程材料，以指导组装、拆解和客体释放。多肽核酸(PNA)是这些聚合物的理想支架，因为它有一个类肽的骨架，可以通过氨基酸侧链实现功能化，并且能够与序列特异地结合到DNA和RNA上。利用之前的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，以推动组装进入胶束。它们展示了在互补DNA或RNA序列存在的情况下对刺激反应的分解，以及细胞通透性和隔离疏水客体分子的能力。在这些激动人心的结果的基础上，拟议的实验旨在：(1)评估侧链结构和图案对组装和小分子结合能力的影响；(2)调查胶束大小和表面属性对细胞摄取和小分子释放的影响；(3)通过化学可寻址的交联链扩大组装的刺激响应控制范围。拟议研究的更广泛影响包括旨在改善本科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来造福公共健康的潜力。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。