Nanomanufacturing of Protein Macromolecular Frameworks Through an Integrated Bioengineering and Computational Approach

需要具有创新功能的新材料来构建新的有用的设备和系统，以丰富我们的生活。由纳米级构建块（通常称为超晶格）构建的有序三维阵列令人兴奋，因为单个构建块之间的相互作用可以产生新的功能。使用蛋白质作为构建模块是一个突破性的新方向，因为蛋白质具有广泛的特性和行为，包括催化和免疫活性，这些通常难以在合成分子中实现。通过传统的蛋白质结晶制造有序的材料是一个费力的过程，而且定制蛋白质晶体结构的能力是有限的。该奖项支持基础研究，以开发通用和可调的方法来制造由蛋白质构成的超晶格材料。这些独特的蛋白质基材料的可用性影响了能源，生物医学和催化等不同行业，从而提高了国家福利。这个项目独特地整合了几个学科，包括材料科学、生物工程和计算建模。在这个项目中，实验和计算方法的整合对计算纳米技术网络（NCN）的研究工作产生了协同作用。除了该项目的科学影响外，它还利用多学科方法，通过获得广泛的技能和知识，并对科学教育产生积极影响，促进包括妇女和少数民族在内的学生参与该项目。研究小组设想，蛋白质笼纳米颗粒和连接蛋白（非共价结合到蛋白质笼上的对称特异性位点）是构建新型蛋白质超晶格（即蛋白质大分子框架）的有希望的基石。蛋白质笼具有中空的球形结构，由不同数量的亚基组成，具有明确的对称特异性位点。研究人员预计，蛋白质笼和连接体之间的特定结合几何形状会导致具有广泛功能的高度规则的网络结构。该研究团队将生物工程和计算建模方法结合起来，开发了一系列具有不同长度和与蛋白质笼结合亲和力的连接分子。通过蛋白质连接器将蛋白质笼连接在一起，它们在几何上受到限制，从而形成高度调节的结构。蛋白质大分子框架的结构可通过选择蛋白质笼和特定的连接蛋白来调节。此外，蛋白质大分子框架内部有两种独特的空间来容纳货物分子。这些是单个蛋白质笼的内部腔和晶格内蛋白质笼之间的间隙。该团队证明，各种货物分子，如酶，可以被封装在蛋白质笼子里。在这个项目中，研究客体分子的可逆掺入和释放，这可能会导致蛋白质大分子框架的实际应用，如药物传递和催化。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

New materials with innovative functionalities are needed to build new and useful devices and systems that enrich our lives. Ordered three-dimensional arrays built from nanoscale building-blocks, often called superlattices, are exciting because new functionalities can emerge from the interactions between individual building-blocks. The use of proteins as building-blocks is a groundbreaking new direction because proteins exhibit a wide range of properties and behavior, including catalytic and immune activities, which are often difficult to realize in synthetic molecules. Making ordered materials by conventional protein crystallization is a laborious procedure and the ability to tailor the structure of protein crystals is limited. This award supports fundamental research to develop versatile and tunable approaches to manufacture superlattice materials constructed of proteins. The availability of these unique protein-based materials impacts diverse industries such as energy, biomedical and catalysis, which advances national welfare. This project uniquely integrates several disciplines including materials science, bioengineering and computational modeling. The integration of experimental and computational approaches in this project impacts research efforts of the Network for Computational Nanotechnology (NCN), synergistically. Alongside the scientific impact of the project, it also leverages the multi-disciplinary approach to promote students, including women and minorities, on this project by acquiring broad skills and knowledge and by providing a positive impact on science education.The research team envisions that protein cage nanoparticles and linker proteins, which bind non-covalently to symmetry-specific sites on the protein cages, are promising building-blocks for constructing a new class of protein superlattices, i.e. protein macromolecular frameworks. Protein cages have hollow spherical architectures composed of a distinct number of subunits with well-defined symmetry-specific sites. The investigators anticipate that specific binding geometries between protein cages and linkers result in highly regular network structures with a wide range of functionalities. The research team integrates bioengineering and computational modeling approaches to develop a range of linker molecules with different lengths and binding affinities to protein cages. By connecting the protein cages together through protein linkers, they are geometrically confined, thus forming highly regulated structures. The structure of the protein macromolecular frameworks is tunable through the selection of protein cages and specific linker proteins. Additionally, protein macromolecular frameworks have two types of unique spaces internally to accommodate cargo molecules. These are interior cavity of individual protein cages and interstitial space between protein cages within the lattice. The team demonstrates that various cargo molecules, such as enzymes, could be encapsulated inside of the protein cages. In this project, reversible incorporation and release of guest molecules are studied, which could lead protein macromolecular frameworks to practical applications such as drug delivery and catalysis.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.