CAREER: Peptide stereocomplexes as dynamic junctions in polymeric biomaterials

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。非技术摘要：开发模仿自然组织的机械、化学和生物特性的材料对推进国家卫生基础设施非常重要。这种材料支持治疗细胞的生长和输送，以修复受损组织，并使研究人员能够研究疾病进展，以确定和评估新的治疗方法。在化学、材料科学、生物学和工程学方面的研究已经产生了一系列可调的组织模拟材料和相关的制造方法。虽然这些生物材料捕捉到了天然组织的各个方面，但仍有令人信服的机会来改进生产工艺和材料性能，以可访问、可扩展的方式全面捕捉天然组织的复杂、高功能特征。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整由合成聚合物和称为多肽的蛋白质片段组成的水膨胀的组织模拟材料的特性。为了激励和引导不同的学生在生物材料研究和教育的前沿从事有价值的职业，这个项目涉及到设计、实施和传播有组织的早期本科研究和教育经验。技术摘要：为了提高生物材料概括天然组织的复杂、高功能特征的能力，重要的是要开发出以一种可访问的、可扩展的方式调整材料性能的方法。该项目的目标是激发立体化学驱动的相互作用，以促进下一代生物材料的制造、控制和功能。立体化学驱动的络合作用或大分子的立体络合作用会使材料的稳定性和热机械性质发生显著变化，但人们对驱动立体络合作用的分子特征以及复杂强度如何影响立体络合材料的性能的了解有限。由于多肽合成可以通过精细控制序列和立体化学来常规生成多肽，具有互补立体化学的多肽为回答这些问题提供了一个理想的材料平台。该项目的目标是(1)确定多肽分子特征(例如长度、电荷和疏水性)如何影响立体络合；以及(2)将多肽立体复合体的分子尺度特征与与多肽立体复合体交联的聚合物水凝胶的整体性质(例如刚性、粘弹性和稳定性)联系起来。建立多肽立体络合的设计规则，并确定这些动态络合物在调节生物材料性能中的作用，是推动立体化学作为控制材料性能的设计参数的关键步骤。作为对研究目标的补充和丰富，教育目标包括构建本科研究的早期阶段，以招募和提供引人入胜的经验，使不同的生物材料研究人员群体获得能力。一个连接多个机构的研究型课程系列将指导学生建立核心能力和网络，以推动他们未来的职业生涯。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。

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.