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：MIT标题：职业：酶功能化聚合物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方面的应用越来越受到关注，其中控制功能蛋白质的纳米结构可以实现材料性能的进步。 嵌段共聚物自组装是在5-50 nm长度尺度上控制蛋白质结构的一种优雅的解决方案，蛋白质嵌段的折叠形状和特异性相互作用导致丰富的新相行为。 该提案将研究融合蛋白以类似于二嵌段共聚物的方式指导球状蛋白自组装的潜力。 融合蛋白的使用将使得能够容易地制备位点特异性缀合物，使用基因工程来控制分子结构。 球状螺旋蛋白质共混物的热力学将被探索，以了解螺旋状蛋白质的序列如何影响其与球状蛋白质的相容性，从而确定一组具有指导自组装潜力的蛋白质。 融合蛋白然后将从靶球状蛋白和有希望的卷曲蛋白序列克隆，以产生能够自组装的蛋白质嵌段共聚物分子。 将开发从水性铸造生产纳米结构凝胶和塑料的加工方法，并将对所得自组装材料进行表征以确定形成的纳米结构的类型。 光谱方法和活性测定将用于评估纳米材料中的蛋白质折叠和功能。 比较粗粒度的蛋白质/聚合物溶液和蛋白质-聚合物共轭自组装的理论将使球螺旋蛋白质融合的自组装的通用热力学得到阐明。 理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化的复杂挑战是材料科学中的一个新障碍，必须解决这些问题以进一步推进生物基材料的知识和应用。 这些球状蛋白质螺旋蛋白质融合自组装的基础研究将提供一种新的方法，材料制备和材料科学和热力学的理解，这些复杂的system.BroADER重要：这一建议将扩大蛋白质为基础的材料的应用，使控制自组装纳米结构的形成使用融合蛋白制备相对容易和廉价的合成和纯化方法。 一个由研究生和本科生研究人员组成的多元化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。 这项研究的重点是基于生物的材料将与努力开发新的方法，将影响本科和高中教学相结合。 将开发一种新的教学方法来教授化学工程入门课程，将材料研究和产品开发的研究结合起来，反映了该专业的现代范围。 该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，影响了全世界这一学科的教育。 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。 将可持续聚合物材料研究与州和国家科学教育标准的核心要求相结合的高中教学法将为这项研究的广泛传播提供一个易于采用的论坛。

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.