Self-Assembled Collagen Networks of Predictable Topologies

ID：MPS/DMR/BMAT（7623）0907599 PI：Case，Martin ORG：佛蒙特大学标题：可预测拓扑结构的自组装胶原蛋白网络智力优势：纤维胶原蛋白是最丰富的哺乳动物蛋白质。 胶原蛋白纤维在体内形成时在原位加工，这种加工引入了不可逆的变化，这些变化不能通过任何物理或化学提取过程来消除。 因此，合成的类似物是非常需要的，作为获得有用量的这种多功能蛋白质用于材料或治疗应用的途径。 该建议提出了一种生物启发的方法，其中胶原蛋白三螺旋自组装，然后被引导到纤维状寡聚化。 关键过程是三螺旋的能量耦合稳定化，伴随着交错多肽寄存器的设置。 该方法使用金属定向组装来形成两种基本结构：封端三聚体和传播三聚体。 封端三聚体通过在N-末端或C-末端（分别为N-封端和C-封端）形成金属络合物而对齐。 它们在另一端呈现“粘性”连接，其中末端残基彼此偏移。 传播的三聚体通过在序列中间的金属络合来组装，并且在与N/C帽互补的任一端呈现交错序列。 N-帽和C-帽三聚体与繁殖物质的适当末端的结合，而不是形成N-帽/C-帽二聚体，是由静电互补性驱动的。 因此，有可能获得比迄今为止可能获得的大得多的原胶原亚基，并且组装过程本身受到更高程度的控制。 更广泛的影响：目前还没有合成胶原蛋白的实用途径，拟议研究的成功可能对再生医学的许多方面产生深远的影响。 PI与佛蒙特大学医学院（UVM）合作，与脊柱重建和血液凝固小组合作，这两项活动都将受益于合成胶原蛋白的可用性。 该项目将支持一名研究生在高度跨学科的环境中工作，以及每年4 - 5名本科生。 预算资金用于支持本科研究生。 作为美国化学学会种子项目的参与者，PI将为经济困难的高中生提供机会，让他们在夏季的几个月里在他的实验室参加一个有意义的研究项目。

ID: MPS/DMR/BMAT(7623) 0907599 PI: Case, Martin ORG: University of VermontTitle: Self-Assembled Collagen Networks of Predictable TopologiesINTELLECTUAL MERIT: Fibrous collagen is the most abundant mammalian protein. Fibers of collagen are processed in situ as they form in vivo, and this processing introduces irreversible changes that cannot be undone by any physical or chemical extraction process. Consequently, a synthetic analog is extremely desirable as a route to obtaining useful quantities of this versatile protein for materials or therapeutic applications. This proposal presents a biologically inspired approach whereby collagen triple helices self-assemble and are then guided to fibrillar oligomerization. The key process is an energetically coupled stabilization of the triple helix with concomitant setting of the staggered polypeptide register. The approach uses metal-directed assembly to form two fundamental structures: capping trimers and propagating trimers. The capping trimers are aligned by metal complex formation at either the N-terminal or the C-terminal ends (N-cap and C-cap, respectively). They present "sticky" connections at the other end, in which the terminal residues are offset from each other. The propagating trimers are assembled by metal complexation in the middle of the sequence, and present staggered sequences at either end that are complementary to the N/C caps. Binding of the N-cap and C-cap trimers to the appropriate ends of the propagating species, rather than forming an N-Cap/C-Cap dimer, is driven by electrostatic complementarity. It is possible consequently to access much larger procollagen subunits than has hitherto been possible, and the assembly process itself is subject to a much higher degree of control. BROADER IMPACTS: There is currently no practical route to a synthetic collagen, and success in the proposed research could have far reaching benefits for many aspects of regenerative medicine. The PI has collaborations with the College of Medicine at the University of Vermont (UVM) with groups working on spinal reconstruction and blood clotting, both of which activities would benefit from the availability of synthetic collagen. The project will support the work of one graduate student in a highly interdisciplinary environment as well as 4 - 5 undergraduates per year. Funds are budgeted for support of the undergraduate research students. As a participant in Project SEED of the American Chemical Society, the PI will provide opportunities for economically disadvantaged high school students to participate in a meaningful research project in his laboratory during the summer months.