Two-dimensional protein arrays: de novo design and applications

二维蛋白质阵列：从头设计和应用

• 批准号: 1401835
• 负责人: Francois Baneyx
• 金额: $ 35万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1401835&HistoricalAwards=false
• 关键词: Two; dimensional; protein; arrays; de

1401835 Baneyx, Francois C. Two dimensional (2D) protein arrays are of considerable interest for the production of advanced materials, devices and systems. For instance, the naturally occurring purple membrane patches of archaeal cells have been exploited for optical information storage; 2D protein layers isolated from archaea and bacteria have been used to produce next generation vaccines and as templates for the fabrication of nanostructured inorganic materials. Yet, these technologies have not evolved beyond proof of concept because they are not robust or scalable, and because neither the geometry, nor the chemistry or assembly of these systems can be precisely controlled from the nano- to the mesoscale. In this work, it is proposed to create an entirely new generation of self-assembled 2D scaffolds that have been designed from the ground up to enable the next generation of advanced materials, biosensors and biodevices. The project seamlessly blends computation, molecular biology, biochemistry, biotechnology, and materials science, and provides a unique opportunity to train students in truly interdisciplinary research. One underrepresented undergraduate student will be paired with a graduate student to broaden participation in science. Results and lessons from the proposed work will be presented to the public and a week-long module on self-assembly will be developed for inclusion in the department's Molecular Engineering curriculum. It is proposed to computationally design a family of proteins that will be capable of robust self-assembly into 2D arrays by fusing protomers from symmetry-compatible oligomers and redesigning interfacial contacts between unit cells. We will delineate and optimize self-assembly conditions for scalable formation of 2D arrays retaining short-range order at the nanoscale but growing over hundreds of micrometers. We will develop approaches to stack these lattices into periodic 3D structures, and apply strategies to control the adsorption and orientation of 2D arrays at technological-relevant interfaces through electrostatic interactions, surface modification and the engineering of solid binding peptides within permissive sites of the structure. And finally, we will explore the potential of these designer 2D lattices as tunable molds for templating inorganic mineralization and as scaffolds for high-density display of enzymes and proteins and for membrane protein crystallization.

1401835 Baneyx，Francois C.二维（2D）蛋白质阵列对于先进材料、装置和系统的生产具有相当大的兴趣。例如，古细菌细胞的天然紫色膜已被用于光学信息存储;从古细菌和细菌中分离的2D蛋白质层已被用于生产下一代疫苗，并作为制造纳米结构无机材料的模板。然而，这些技术还没有发展到超出概念验证的程度，因为它们不稳健或可扩展，并且因为这些系统的几何形状、化学性质或组装都不能从纳米级精确控制到中尺度。在这项工作中，提出了创建全新一代的自组装2D支架，这些支架是从头开始设计的，以实现下一代先进材料，生物传感器和生物设备。该项目无缝融合计算，分子生物学，生物化学，生物技术和材料科学，并提供了一个独特的机会，培养学生在真正的跨学科研究。一名代表性不足的本科生将与一名研究生配对，以扩大对科学的参与。拟议工作的结果和经验教训将向公众展示，并将开发一个为期一周的自组装模块，以纳入该部门的分子工程课程。 它提出了计算设计一个家庭的蛋白质，将能够强大的自组装成2D阵列，融合原聚体从兼容的寡聚体和重新设计单位细胞之间的界面接触。我们将描绘和优化自组装条件，以可扩展地形成二维阵列，保持纳米级的短程秩序，但增长超过数百微米。我们将开发将这些晶格堆叠成周期性3D结构的方法，并通过静电相互作用，表面改性和结构允许位点内的固体结合肽的工程设计，应用策略来控制技术相关界面处2D阵列的吸附和取向。最后，我们将探索这些设计师的2D晶格作为模板无机矿化的可调模具和作为高密度显示酶和蛋白质以及膜蛋白质结晶的支架的潜力。