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Engineered Organic Color Centers for Profiling Protein-Carbohydrate Recognition

用于分析蛋白质-碳水化合物识别的工程有机颜色中心

基本信息

批准号：
1917513
负责人：
Geyou Ao
金额：
$ 34.69万
依托单位：
Cleveland State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917513&HistoricalAwards=false
关键词：
Engineered Organic Color Centers Profiling

项目摘要

Protein-carbohydrate recognitions are crucial events in many biological processes including cell-cell communication, immune response, cancer development and metastasis. Understanding specific interactions between carbohydrates and carbohydrate-binding proteins has been a challenging task due to the lack of versatile probes. Organic color centers created on nanomaterial hosts with precise optical and carbohydrate functionalities are uniquely suited to profile protein-carbohydrate recognition, which can lead to clarifying functions of both molecules and their underlying molecular mechanism and discovering therapeutic and diagnostic mechanism as well. This project will promote the progress in science by advancing fundamental understanding of structure-property relationships of engineered organic color centers with biological functionalities and establishing the probing behavior of carbohydrate-functionalized color centers for specific biological targets in either physiological and pathological pathways. In addition to advancing an emerging frontier across nanotechnology, chemistry, glycoscience, and engineering, this work will positively impact the well-being of society. First, this work will contribute to the development of the next-generation multicolor fluorescent probes with precise functionalities for biomedical research and applications. Second, this project will provide exciting opportunities to students of all backgrounds through promoting engaged learning via hands-on research in an evolving interdisciplinary field of nanomaterial science and technology and glycosciences. It will further support the advancement of a broadly inclusive, next-generation science and engineering workforce, particularly in bio-nanotechnology.This project will focus on probing specific interactions between carbohydrates and proteins by engineered organic color centers with the goal of achieving new nanomaterial tools to detect targeted molecular interactions in biological processes with enhanced sensitivity and selectivity. The proposed color centers will be created through covalently functionalizing the sidewall of semiconducting, pure-chirality single-wall carbon nanotubes via oriented immobilization of glycopolymers that closely mimic the natural glycan structures and functions. There are many advantages for the proposed color centers. First, chirality-defined carbon nanotube hosts have defined structures and properties and color centers created on nanotubes further tune light in the near-infrared regime that has attenuated autofluorescence and deep tissue penetration, providing the ideal condition for high contrast fluorescence detection in complicated biological samples. Second, pure-chirality carbon nanotubes promote advances in ultra-low dose, high efficiency nanomedicines. Third, biomimetic, precision synthesized glycopolymers mimic the three-dimensional display of carbohydrates on the cell surfaces, thus warrant enhanced sensitivity and selectivity for proteins. Particularly, the proposed work will involve i) synthesizing organic color centers using galactose-containing glycopolymers with different carbohydrate ligand densities, ii) determining how the galactose pendent groups of glycopolymers mediate the specific interaction of color centers with asialoglycoprotein receptor of human hepatoma cells, and iii) assessing the basal toxicity and functionality of organic color centers for selectively identifying human hepatoma cells utilizing both two-dimensional and three-dimensional cell cultures. Here, microarray three-dimensional bioprinting of cell cultures provides in vivo-like microenvironments to better asses the toxicity and selectivity of nanomaterials-based color centers, which could be used as biocompatible, cancer cell-targeting multicolor fluorescent probes. Optical properties of engineered organic color centers and their specific interactions with proteins and human liver cancer cells will be characterized primarily by optical spectroscopy of color centers, high-content imaging assays, and near-infrared fluorescence imaging. The combinatorial diversity of nanotube structure and glycopolymer configuration offers vast potential for chemical innovation and biochemical sensing and imaging advancement. If successful, this work will provide a transformative approach to study the carbohydrate recognition in biology that is essential to uncover molecular mechanisms of many biological processes. This work will also open up possibilities to create a new class of multicolor fluorescent probes with distinct properties that are previously never achieved for many applications, such as biosensing and bioimaging.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.

蛋白质-碳水化合物代谢是许多生物学过程中的关键事件，包括细胞-细胞通讯、免疫应答、癌症发展和转移。由于缺乏通用的探针，了解碳水化合物和碳水化合物结合蛋白之间的特异性相互作用一直是一项具有挑战性的任务。在具有精确光学和碳水化合物功能的纳米材料主体上产生的有机色心独特地适合于分析蛋白质-碳水化合物识别，这可以导致澄清两种分子的功能及其潜在的分子机制，并发现治疗和诊断机制。该项目将通过推进对工程有机色心与生物功能的结构-性质关系的基本理解，并建立碳水化合物功能化色心在生理和病理途径中针对特定生物靶点的探测行为，促进科学进步。除了推进纳米技术，化学，糖科学和工程学的新兴前沿外，这项工作还将对社会福祉产生积极影响。首先，这项工作将有助于开发下一代具有精确功能的荧光探针，用于生物医学研究和应用。其次，该项目将通过在纳米材料科学技术和糖科学的不断发展的跨学科领域的实践研究促进参与式学习，为所有背景的学生提供令人兴奋的机会。该项目将进一步支持广泛包容的下一代科学和工程人才的发展，特别是在生物纳米技术方面。该项目将重点关注通过工程有机色心探测碳水化合物和蛋白质之间的特定相互作用，目标是实现新的纳米材料工具，以更高的灵敏度和选择性检测生物过程中的目标分子相互作用。提出的色心将通过共价官能化的半导体，纯手性单壁碳纳米管的侧壁，通过定向固定的糖共聚物，密切模仿天然聚糖的结构和功能。所提出的色心有许多优点。首先，手性限定的碳纳米管主体具有限定的结构和性质，并且在纳米管上产生的色心进一步调谐近红外区中的光，该近红外区具有衰减的自发荧光和深层组织穿透，为复杂生物样品中的高对比度荧光检测提供理想条件。其次，纯手性碳纳米管促进了超低剂量、高效纳米医学的进步。第三，仿生，精确合成的糖共聚物模拟碳水化合物在细胞表面的三维显示，从而保证对蛋白质的灵敏度和选择性增强。特别地，所提出的工作将涉及i）使用具有不同碳水化合物配体密度的含半乳糖的糖共聚物合成有机色心，ii）确定糖共聚物的半乳糖侧基如何介导色心与人肝癌细胞的脱唾液酸糖蛋白受体的特异性相互作用，和iii）评估有机色心的基础毒性和功能性，用于利用两种-三维和三维细胞培养。在这里，细胞培养物的微阵列三维生物打印提供了体内类似的微环境，以更好地评估基于纳米材料的色心的毒性和选择性，其可用作生物相容性的癌细胞靶向荧光探针。工程有机色心的光学性质及其与蛋白质和人肝癌细胞的特异性相互作用将主要通过色心的光谱学、高含量成像测定和近红外荧光成像来表征。纳米管结构和糖聚合物结构的组合多样性为化学创新以及生化传感和成像进步提供了巨大的潜力。如果成功，这项工作将提供一种变革性的方法来研究生物学中的碳水化合物识别，这对于揭示许多生物过程的分子机制至关重要。这项工作也将开辟可能性，创造一个新的类别的荧光探针，具有独特的性能，以前从来没有实现过的许多应用，如生物传感和生物成像。这个奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的知识价值和更广泛的影响审查标准。