CAREER: Peptide stereocomplexes as dynamic junctions in polymeric biomaterials

职业：肽立体复合物作为聚合物生物材料中的动态连接

• 批准号: 2143647
• 负责人: Rachel Letteri
• 金额: $ 56.4万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143647&HistoricalAwards=false
• 关键词: CAREER; Peptide; stereocomplexes; dynamic; junctions

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Non-technical Abstract:Developing materials that mimic the mechanical, chemical, and biological properties of natural tissue is important for advancing national health infrastructure. Such materials support the growth and delivery of therapeutic cells for repair of damaged tissue and enable researchers to study disease progression for identification and evaluation of new treatment approaches. Research in chemistry, materials science, biology, and engineering has produced a range of tunable tissue-mimicking materials and associated fabrication methods. While these biomaterials capture various aspects of native tissue, there remain compelling opportunities to improve both the production processes and materials properties to comprehensively capture the complex, highly functional features of native tissue in an accessible, scalable manner. This project will employ advanced synthetic and characterization techniques to develop new ways to prepare and tune the properties of water-swollen, tissue-mimetic materials composed of synthetic polymers and protein fragments called peptides. To inspire and guide a diverse cohort of students towards rewarding careers at the forefront of biomaterials research and education, this project involves the design, implementation, and dissemination of structured early-stage undergraduate research and educational experiences. Technical Abstract:To advance the ability of biomaterials to recapitulate the complex, highly functional characteristics of native tissue, it is important to develop ways to tune materials properties in an accessible, scalable manner. The goal of this project is to invoke stereochemistry-driven interactions to advance the manufacturing, control, and function of next-generation biomaterials. Stereochemistry-driven complexation, or ‘stereocomplexation’ of macromolecules produces marked changes in stability and thermomechanical properties of materials, yet there is limited understanding about the molecular features driving stereocomplexation and how complex strength impacts the properties of stereocomplexed materials. Since peptide synthesis enables routine generation of peptides with exquisite control of sequence and stereochemistry, peptides with complementary stereochemistry provide an ideal materials platform for answering these questions. The objectives of this project are to (1) determine how peptide molecular features (e.g., length, charge, and hydrophobicity) impact stereocomplexation; and (2) connect molecular-scale features of peptide stereocomplexes to the bulk properties (e.g., stiffness, viscoelasticity, and stability) of polymeric hydrogels cross-linked with peptide stereocomplexes. Establishing design rules for peptide stereocomplexation and determining the roles of these dynamic complexes in modulating biomaterials properties represent critical steps to advancing stereochemistry as a design parameter to control materials properties. Complementing and enriching the research objectives, educational objectives include structuring the early stages of undergraduate research to recruit and provide engaging experiences that empower a diverse group of biomaterials researchers. A research-based course series bridging multiple institutions will guide students in building core competencies and networks to propel their future careers.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.

该奖项全部或部分由2021年美国救援计划法案（公法117-2）资助。非技术摘要：开发模仿天然组织的机械，化学和生物特性的材料对于推进国家卫生基础设施非常重要。 这些材料支持治疗细胞的生长和递送，用于修复受损组织，并使研究人员能够研究疾病进展，以识别和评估新的治疗方法。 化学、材料科学、生物学和工程学的研究已经产生了一系列可调的仿组织材料和相关的制造方法。 虽然这些生物材料捕获了天然组织的各个方面，但仍然存在改善生产工艺和材料性能的迫切机会，以可访问的、可扩展的方式全面捕获天然组织的复杂的、高度功能性的特征。 该项目将采用先进的合成和表征技术，开发新的方法来制备和调节由合成聚合物和称为肽的蛋白质片段组成的水溶胀，组织模拟材料的性能。 为了激励和引导不同的学生群体在生物材料研究和教育的最前沿获得有价值的职业，该项目涉及结构化早期本科研究和教育经验的设计，实施和传播。技术摘要：为了提高生物材料概括天然组织的复杂、高度功能性特征的能力，重要的是要开发以可访问、可扩展的方式调整材料特性的方法。 该项目的目标是调用立体化学驱动的相互作用，以推进下一代生物材料的制造，控制和功能。 大分子的立体化学驱动的络合或“立体络合”在材料的稳定性和热机械性质方面产生显著变化，但对驱动立体络合的分子特征以及络合强度如何影响立体络合材料的性质的理解有限。 由于肽合成能够常规生成具有精确控制序列和立体化学的肽，具有互补立体化学的肽为回答这些问题提供了理想的材料平台。 该项目的目标是（1）确定肽分子特征（例如，长度、电荷和疏水性）影响立体络合;和（2）将肽立体络合物的分子尺度特征与整体性质（例如，刚性、粘弹性和稳定性）。 建立肽立体络合的设计规则和确定这些动态复合物在调节生物材料性质中的作用代表了推进立体化学作为控制材料性质的设计参数的关键步骤。 补充和丰富的研究目标，教育目标包括构建本科研究的早期阶段，招募和提供参与的经验，使生物材料研究人员的多元化群体。 一个以研究为基础的课程系列将连接多个机构，引导学生建立核心能力和网络，以推动他们未来的职业生涯。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。