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Protein framework for manipulating nanoparticles and enzymes: from capsules to arrays

用于操纵纳米粒子和酶的蛋白质框架：从胶囊到阵列

基本信息

批准号：
1905203
负责人：
Ivan Dmochowski
金额：
$ 54万
依托单位：
University of Pennsylvania
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：
2019-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1905203&HistoricalAwards=false
关键词：
Protein framework manipulating nanoparticles enzymes

项目摘要

Professors Ivan J. Dmochowski and Jeffery G. Saven of the University of Pennsylvania are supported by the Macromolecular, Supramolecular and Nanochemistry Program of the Division of Chemistry to elucidate how hollow and cage-like proteins can form nano-containers to encapsulate nanoparticles and other proteins such as enzymes. Experimental approaches and theoretical methods are combined to understand these molecular systems and to engineer molecular containers for specific cargos and applications. An important aim of the project is to develop chemistries and methods to link single containers together to form three-dimensional microarray structures. The goal is to engineer microarrays for specific applications in catalysis, and to integrate judicially designed microarrays in functional devices, such as biosensors and enzyme cargo delivery systems. Cage-like ferritin proteins provide a unique model system for studying bio-nano supramolecular assembly, and the modular "molecular capsule-to-array" concept provides a versatile platform for addressing many materials chemistry challenges in nanotechnology and biotechnology. Ordered hierarchical assembly of small nanostructures into larger, well-structured arrays can deliver desirable materials properties, self-assembly, and processability. Graduate and undergraduate students, including students from the University of Puerto Rico, are receiving multidisciplinary training through this collaborative research. In addition, laboratory and classroom activities targeting middle, and high school students are being developed. These activities are subjected to evaluation and best practices are prepared for publication in chemical education journals.Ferritin proteins encapsulate appropriately sized and liganded inorganic nanoparticles or super-positively-charged proteins in native-like assemblies. The research team aims to elucidate how cage-like proteins, such as thermophilic ferritin from A. fulgidus (AfFtn), encapsulate various nonbiological and biological cargo to form stable, molecularly precise nano-containers. Computational protein design identifies amino acid mutations that enhance the stability of ferritin capsules. Design and modeling are also applied to guest species, such as super-positively-charged enzymes, to explore determinants of efficient ferritin encapsulation. Molecular simulations provide insight on the structure and dynamics of ferritin-nanoparticle and ferritin-protein interactions. Guided by computational design, an expanded set of inorganic nanoparticles and enzyme cargos are being identified and assessed. Experimental approaches range from the creation and processing of recombinant proteins to the biophysical characterization of ferritin assembly and encapsulation in solution and in the solid-state. An important goal is to link AfFtn capsules at engineered and structurally well-determined attachment sites to form well-defined arrays. Among several strategies to be pursued is the incorporation of divalent cation binding sites at the three-fold symmetric ferritin pores and subsequent formation of arrays with bis-hydroxamate linkers.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.

教授伊万J. Dmochowski和杰弗里G. Saven的研究得到了化学系大分子，超分子和纳米化学项目的支持，以阐明中空和笼状蛋白质如何形成纳米容器来封装纳米颗粒和其他蛋白质，如酶。实验方法和理论方法相结合，以了解这些分子系统和工程分子容器的特定货物和应用。该项目的一个重要目的是开发化学和方法，将单个容器连接在一起，形成三维微阵列结构。其目标是设计用于催化的特定应用的微阵列，并将合理设计的微阵列集成到功能设备中，如生物传感器和酶货物递送系统。笼状铁蛋白为研究生物纳米超分子组装提供了一个独特的模型系统，模块化的“分子胶囊到阵列”概念为解决纳米技术和生物技术中的许多材料化学挑战提供了一个通用的平台。将小纳米结构有序分级组装成较大的结构良好的阵列可以提供所需的材料性质、自组装和可加工性。研究生和本科生，包括来自波多黎各大学的学生，正在通过这项合作研究接受多学科培训。此外，正在开展针对初中和高中学生的实验室和课堂活动。这些活动将接受评估，最佳实践将在化学教育期刊上发表。铁蛋白将适当大小和配体的无机纳米粒子或带超正电荷的蛋白质包裹在天然组装体中。该研究小组的目标是阐明笼状蛋白，如嗜热铁蛋白从A。fulgidus（AfFtn）封装各种非生物和生物货物以形成稳定的、分子精确的纳米容器。计算蛋白质设计识别增强铁蛋白胶囊稳定性的氨基酸突变。设计和建模也适用于客体物种，如超正电荷的酶，探索有效的铁蛋白封装的决定因素。分子模拟提供了铁蛋白纳米粒子和铁蛋白相互作用的结构和动力学的见解。在计算设计的指导下，一组扩大的无机纳米粒子和酶货物正在被识别和评估。实验方法的范围从重组蛋白的产生和加工到铁蛋白组装的生物物理表征以及溶液和固态中的封装。一个重要的目标是将AfFtn胶囊连接在工程化的和结构明确的附着位点，以形成明确定义的阵列。其中几个策略要追求的是二价阳离子结合位点的三重对称铁蛋白孔和随后形成的阵列与bis-hydroxamate linkers.This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。