Self-Assembly of Dynamic, Functional Protein Matrices

描述(申请人提供)：亚微米级材料的结构控制可以提供对广泛的材料性能的精细控制，包括孔隙率、机械性能、对生物和非生物分子的亲和力以及配体的呈现。对这些特性的控制将影响从材料科学到生物技术领域的广泛应用，包括生物传感器开发和组织工程。这一建议的指导假设是，特定的分子间相互作用，如蛋白质四聚化和配体诱导的构象变化，可以用来设计自组装成动态二维和三维材料的蛋白质单元。我建议识别候选蛋白质，根据它们亚基间的相互作用和对称性，最有可能组装成可预测的二维或三维结构。然后，这些蛋白质的亚基将被连接起来，以允许自组装成具有可控纳米级结构的扩展蛋白质基质。蛋白质构建块之间的连接区将被设计为包含因配体结合而发生构象变化以创建动态结构的单元，或调节细胞黏附以创建细胞培养和组织工程底物的单元。

DESCRIPTION (provided by applicant): Structural control of materials on the sub-micron scale may afford exquisite control over a broad spectrum of material properties, including porosity, mechanical properties, affinity for biological and non-biological molecules, and presentation of ligands. Control over these characteristics would influence a wide variety of applications in fields ranging from materials science to biotechnology, including biosensor development and tissue engineering. The guiding hypothesis of this proposal is that specific intermolecular interactions, such as protein tetramerization and ligand-induced conformational changes, can be employed to design protein units that self-assemble into dynamic 2-dimensional and 3-dimensional materials. I propose to identify candidate proteins that, based on their inter-subunit interactions and symmetry, are most likely to assemble into predictable 2-dimensional or 3-dimensional structures. Subunits of these proteins will then be linked to allow for self assembly into an extended protein matrix with controlled nanometer-scale structure. The linkage regions between the protein building blocks will be designed to contain units that undergo conformational changes in response to ligand binding to create dynamic structures, or units that mediate cell adhesion to create substrates for cell culture and tissue engineering.