Nanoscale energy production for implantable medical devices

用于植入式医疗设备的纳米级能量生产

• 批准号: 8306909
• 负责人: ALEXANDER J TRAVIS
• 金额: $ 76.23万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306909
• 关键词: Address; Binding; Biological; Coupled; Data; Devices; Enzymes; Germ; Glucose; Glycolysis; Hybrids; Mechanics; Medical; Medical Device; Modeling; Natural regeneration; Pathway interactions; Pharmaceutical Preparations; Physiology; Production; Recombinants; Rest; Series; System; Technology; Testing; Tissues; Work; design; enzyme activity; implantable device; innovation; nanobiotechnology; nanodevice; nanoscale; protein function; sperm cell

Nanobiotechnology offers the possibility of new forms of medical treatments, such as implantable devices that carry out biological or mechanical functions, or deliver drugs to specific tissues. Because proteins function so efficiently at this small scale, they will likely be major components of nanodevices. However, a number of important obstacles must be overcome for nanodevices to realize their potential. One of the most critical problems is how to supply implantable nanodevices with energy. Our work on the physiology of mammalian sperm has inspired us with a strategy to address this important issue. Sperm generate ATP throughout the flagellar principal piece by using glycolytic enzymes tethered to a cytoskeletal support by means of germ cellspecific targeting domains. We hypothesize that by identifying and modifying these domains, we can generate recombinant glycolytic enzymes that can be bound to a support and retain function. As proof of principle, we have made modified forms of the first two enzymes in this pathway, and show their activities in series when coupled to the same support. To our knowledge, this is the first demonstration of sequential enzymatic activities in a multi-step pathway on a hybrid organic-inorganic device. These data also support our hypothesis that sperm provide a natural model of how to produce ATP locally on nanodevices. We propose to construct similarly modified recombinant forms of the rest of the enzymes of glycolysis, as well as an additional enzyme that will be needed for co-enzyme regeneration. We shall then test the activities of these enzymes individually, in sub-assemblies, and in series on single supports in our effort to design a system through which implantable nanodevices can produce their own energy from freely available circulating glucose. If successful, our innovative strategy will produce an enabling technology that should advance a variety of medical applications for nanobiotechnology.

纳米生物技术提供了新形式的医学治疗的可能性，例如植入式设备 它们执行生物或机械功能，或将药物输送到特定组织。因为蛋白质的功能 在如此小的尺度上如此有效，它们将可能成为纳米器件的主要组成部分。但若干 纳米器件要实现其潜力，就必须克服重要的障碍。一个最关键的 问题是如何为可植入的纳米装置提供能量。我们对哺乳动物生理学的研究 精子启发了我们解决这一重要问题的策略。精子产生ATP的整个过程 鞭毛主片通过使用糖酵解酶系到细胞骨架支持，通过生殖细胞特异性 靶向域。我们假设，通过识别和修改这些域，我们可以生成 重组糖酵解酶可以结合到支持物上并保留功能。作为原则的证明，我们 已经对这一途径中的前两种酶进行了修饰，并在下列情况下显示出它们的活性： 连接到同一个支架上。据我们所知，这是第一次证明顺序酶促反应， 在杂化有机-无机装置上的多步途径中的活性。这些数据也支持了我们的假设 精子提供了一个天然的模型，可以在纳米设备上局部产生ATP。 我们建议构建糖酵解其余酶的类似修饰的重组形式， 以及辅酶再生所需的额外酶。然后，我们将测试活动 这些酶单独，在子组件，并在单一的支持，在我们的努力，设计一个系列 可植入纳米设备可以通过自由循环产生自己的能量的系统 葡萄糖如果成功的话，我们的创新战略将产生一种使能技术， 纳米生物技术的各种医疗应用。