CAREER: Self-Assembly of Fusion Proteins to Form Biofunctional Materials

ID: MPS/DMR/BMAT(7623) 1253306 PI：奥尔森，布拉德利ORG: MITTitle：职业生涯：自组装融合蛋白形成生物功能材料酶功能化高分子材料在生物医学材料、传感、生物催化、能量转换和化学试剂解毒等领域的应用越来越受到关注，控制功能蛋白的纳米结构可以提高材料的性能。嵌段共聚物自组装是一种在5-50 nm长度范围内控制蛋白质结构的优雅解决方案，蛋白质嵌段的折叠形状和特定的相互作用导致了丰富的新相行为。本提案将研究融合蛋白的潜力，以类似于二嵌段共聚物的方式指导球状蛋白的自组装。融合蛋白的使用将使位点特异性偶联物的制备变得容易，利用基因工程来控制分子结构。将探索球形-线圈蛋白混合物的热力学，以了解线圈状蛋白的序列如何影响其与球形蛋白的混溶性，从而确定一组具有指导自组装潜力的蛋白质。然后从目标球状蛋白和有前途的线圈蛋白序列中克隆融合蛋白，以生产能够自组装的蛋白质嵌段共聚物分子。将开发从水性铸件中生产纳米结构凝胶和塑料的加工方法，并对所产生的自组装材料进行表征，以确定形成的纳米结构的类型。光谱学方法和活性分析将用于评估纳米材料中的蛋白质折叠和功能。与蛋白质/聚合物溶液和蛋白质-聚合物共轭自组装的粗粒度理论进行比较，将使球形线圈蛋白质融合自组装的普遍热力学得以阐明。了解蛋白质折叠和特定相互作用如何影响软材料中的纳米结构是材料科学中一个新兴的障碍，必须解决这个复杂的挑战，以进一步推进生物基材料的知识和应用。这些关于球形蛋白-线圈蛋白融合自组装的基础研究将为材料制备提供新的方法，并为理解这些复杂系统的材料科学和热力学提供新的思路。更广泛的影响：本提案将扩大蛋白质基材料的应用，通过相对简单和廉价的合成和纯化方法制备融合蛋白，使控制自组装纳米结构的形成成为可能。一个由研究生和本科生组成的多元化研究团队将对该项目进行研究，为不同教育水平的工程师提供宝贵的培训经验。这项以生物材料为基础的研究将与开发影响本科和高中教学的新方法相结合。化学工程导论课程的教学将采用一种新的教学方法，将材料研究和产品开发的研究结合起来，以反映该专业的现代范围。本提案的本科教育目标改变了普遍接受的化学工程入门课程的教学，影响了世界范围内该学科的教育。与当地高中教师合作，还将开发可持续聚合物和生物材料单元的教材以及聚合物材料的演示，以将对这一研究领域的兴奋转化为中学生。将可持续高分子材料研究与国家和国家科学教育标准的核心要求相结合的高中教学方法，将为这一研究的广泛传播提供一个容易采用的论坛。

ID: MPS/DMR/BMAT(7623) 1253306 PI: Olsen, Bradley ORG: MITTitle: CAREER: Self-Assembly of Fusion Proteins to Form Biofunctional MaterialsINTELLECTUAL MERIT: Enzyme-functionalized polymeric materials have attracted increasing attention for applications in biomedical materials, sensing, biocatalysis, energy conversion, and chemical agent detoxification, where controlling the nanostructure of the functional proteins can enable advances in material performance. Block copolymer self-assembly is an elegant solution to control protein structure on the 5-50 nm length scale, and the folded shapes and specific interactions of the protein blocks lead to rich new phase behavior. This proposal will investigate the potential of fusion proteins to direct the self-assembly of globular proteins in a manner analogous to diblock copolymers. The use of fusion proteins will enable the easy preparation of site-specific conjugates, using genetic engineering to control molecular structure. The thermodynamics of globular-coil protein blends will be explored to understand how the sequence of a coillike protein affects its miscibility with globular proteins, allowing a set of proteins with potential for directing self-assembly to be identified. Fusion proteins will then be cloned from target globular proteins and promising coil protein sequences in order to produce protein block copolymer molecules capable of self-assembly. Processing methods to produce nanostructured gels and plastics from aqueous casting will be developed, and the resulting self-assembled materials will be characterized to identify the type of nanostructures formed. Spectroscopic methods and activity assays will be used to assess protein fold and function within the nanomaterials. Comparison to coarse-grained theories for protein/polymer solutions and protein-polymer conjugate self-assembly will enable the universal thermodynamics of self-assembly for globular-coil protein fusions to be elucidated. The complex challenges of understanding how protein fold and specific interactions affect nanostructuring in soft materials is an emerging obstacle in materials science that must be addressed to further advance knowledge and application of bio-based materials. These fundamental studies of globular protein-coil protein fusion self-assembly will provide both a new method for material preparation and an understanding of the materials science and thermodynamics of these complex systems.BROADER IMPACTS: This proposal will expand the application of protein-based materials by enabling control over self-assembled nanostructure formation using fusion proteins prepared by relatively easy and inexpensive synthesis and purification methods. A diverse team of graduate and undergraduate researchers will perform research on this project, providing valuable training experiences to engineers at several educational levels. This research focus on biologically-based materials will be integrated with efforts to develop novel methods that will impact both undergraduate and high school teaching. A new pedagogy will be developed for teaching the introductory Chemical Engineering course, integrating the study of materials research and product development that reflects the modern scope of the profession. The undergraduate level educational objectives of this proposal transform the teaching of the universally accepted introductory chemical engineering course, impacting education in this discipline worldwide. In collaboration with local high school teachers, teaching materials for a unit on sustainable polymers and biomaterials and demonstrations of polymer materials will also be developed to translate excitement about this research area to secondary school students. A high school pedagogy that integrates sustainable polymer materials research to teach core requirements of state and national science education standards will provide an easily adopted forum for the broad dissemination of this research.