Self-Assembly of Dynamic, Functional Protein Matrices

动态功能蛋白基质的自组装

• 批准号: 6690792
• 负责人: WILLIAM L. MURPHY
• 金额: $ 4.16万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-03 至 2005-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6690792
• 关键词: atomic force microscopy; cell adhesion; conformation; fibroblasts; intermolecular interaction; matrix assisted laser desorption ionization; molecular assembly /self assembly; nanotechnology; postdoctoral investigator; protein binding; protein structure; transmission electron microscopy

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.

描述（由申请人提供）：在亚微米尺度上对材料进行结构控制可以提供对广泛的材料性质的精细控制，包括孔隙率、机械性质、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（包括生物传感器开发和组织工程）等领域的各种应用。该建议的指导假设是，特定的分子间相互作用，如蛋白质四聚体和配体诱导的构象变化，可以用来设计蛋白质单元，自组装成动态的二维和三维材料。我建议，以确定候选蛋白质，根据其亚基间的相互作用和对称性，是最有可能组装成可预测的2维或3维结构。然后，这些蛋白质的亚基将被连接，以允许自组装成具有受控纳米级结构的扩展蛋白质基质。蛋白质结构单元之间的连接区域将被设计为包含响应于配体结合而经历构象变化以产生动态结构的单元，或介导细胞粘附以产生用于细胞培养和组织工程的底物的单元。