CAREER: Elucidating the Synergistic Nanoscale and Carbohydrate Interactions of Glyconanomaterials with Bacterial Proteins, Toxins, and Cells

碳水化合物介导的相互作用涉及许多细胞事件，包括免疫反应和感染。具有碳水化合物功能的纳米材料在多个长度尺度上的控制制造将使许多应用成为可能，例如蛋白质和毒素的多功能传感，以及针对广谱细菌、病毒和真菌的多功能抗菌涂层。该职业奖支持基础研究，为建立生物聚合物-氮化硼纳米复合材料提供框架，用于从感知微生物病原体到减轻感染传播的多功能抗菌应用。此外，氮化硼纳米材料卓越的机械、热学、电学和物理化学性能将使多功能保护涂层具有电绝缘、导热和吸收紫外线的功能。这项研究将与纳米技术和糖科学核心领域的教育和推广活动紧密结合。该项目将为当地初中和高中学生和教师提供互动式研讨会和讲习班。此外，它将允许形成一个高度跨学科的纳米技术课程，重点是生物纳米材料和应用开发。这些活动结合起来，将同时推进科学发现，培养一支广泛包容、多样化的科学和工程人才队伍。碳水化合物修饰的纳米材料（称为糖异材料）与微生物的协同纳米尺度和碳水化合物相互作用机制在很大程度上是未知的。本研究将验证糖异物质与碳水化合物结合细菌蛋白和毒素的协同相互作用可以增强细菌粘附、毒素抑制和细胞膜破坏的特异性和多价性这一广泛假设。具体来说，具有可调碳水化合物结构的糖共聚物模仿天然糖缀合物的功能，将与一维氮化硼纳米管和二维氮化硼纳米片非共价络合。氮化硼支架的纳米级尺寸和形状允许多价配体显示和聚合物的不同构象排列。这将显著增强碳水化合物介导的相互作用的结合亲和力，甚至可以发现糖异物材料特有的与微生物的纳米结构依赖的相互作用。利用光谱学、小角度x射线散射和电子显微镜研究糖共聚物-氮化硼配合物与细菌蛋白质和毒素的分子相互作用。由氮化硼-糖基共聚物络合物制成的坚固涂层的抗菌性能将通过抗菌试验进行研究。这项研究将阐明糖共聚物-氮化硼纳米系统的机理行为，并将为制造广泛应用的糖共聚物材料提供一种变革性的方法，包括用于改善室内空气质量的抗菌涂层和微生物的生物传感器。通过创新的纳米技术课程和外展活动，将研究和教育结合起来，将为增加不同背景的工程学生建立一个平台。结合起来，这个CAREER项目将同时推进科学发现和下一代科学家和工程师。该奖项反映了美国国家科学基金会的法定使命，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。

Carbohydrate-mediated interactions are involved in many cellular events, including immune responses and infections. Controlled fabrication of nanomaterials with carbohydrate functionalities across multiple length scales will enable many applications, such as versatile sensing of proteins and toxins as well as multifunctional, antimicrobial coatings against a broad spectrum of bacteria, viruses, and fungi. This CAREER award supports fundamental research to provide the framework for establishing biopolymer-boron nitride nanomaterial hybrids for multifunctional antimicrobial applications from sensing microbial pathogens to mitigating the spread of infections. In addition, exceptional mechanical, thermal, electrical, and physicochemical properties of boron nitride nanomaterials will enable multifunctional protective coatings that are electrically insulating, thermally conductive, and absorb ultraviolet light. This research will be closely integrated into educational and outreach activities in the core areas of nanotechnology and glycoscience. This project will enable the offering of interactive seminars and workshops for local middle and high school students and teachers. In addition, it will allow the formation of a highly interdisciplinary nanotechnology course focusing on bionanomaterials and applications development. Combined, these activities will simultaneously advance scientific discovery and train a broadly inclusive, diverse, science and engineering workforce.Synergistic nanoscale and carbohydrate interaction mechanisms of carbohydrate-decorated nanomaterials (known as glyconanomaterials) with microbes are largely unknown. This research will test the broad hypothesis that the synergistic interactions of glyconanomaterials with carbohydrate-binding bacterial proteins and toxins can enhance specificity and multivalency for bacterial adhesion, toxin inhibition, and cell membrane disruption. Specifically, glycopolymers with tunable carbohydrate structures mimicking the functions of naturally occurring glycoconjugates will be complexed noncovalently with one-dimensional boron nitride nanotubes and two-dimensional boron nitride nanosheets. The nanoscale size and shape of boron nitride scaffolds allow multivalent ligand display and distinct conformational arrangement of polymers. This will significantly amplify the binding affinity of carbohydrate-mediated interactions and even enable the discovery of nanostructure-dependent interactions with microbes that are unique to glyconanomaterials. Molecular interactions of glycopolymer-boron nitride complexes with bacterial proteins and toxins will be investigated by optical spectroscopy, small-angle X-ray scattering, and electron microscopy. The antibacterial property of robust coatings from glycopolymer-boron nitride complexes will be investigated by antimicrobial assays. This research will illuminate the mechanistic behavior of glycopolymer-boron nitride nanosystems and will offer a transformative approach to fabricate glyconanomaterials for a broad range of applications, including antimicrobial coatings for improving indoor air quality and biosensors of microbes. The integration of research and education through an innovative nanotechnology course and outreach activities will establish a platform for increasing the pipeline of engineering students of diverse backgrounds. Combined, this CAREER project will simultaneously advance scientific discovery and the next generation of scientists and engineers.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.