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: 7939732
• 负责人: ALEXANDER J TRAVIS
• 金额: $ 77万
• 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/7939732
• 关键词: Address; Binding; Biological; Coupled; Data; Devices; Enzymes; Germ; Glucose; Glycolysis; Hybrids; Knowledge; Mechanics; Medical; Medical Device; Modeling; Natural regeneration; Pathway interactions; Pharmaceutical Preparations; Physiology; Production; Recombinants; Rest; Series; System; Technology; Testing; Tissues; Work; abstracting; design; enzyme activity; implantable device; innovation; nanobiotechnology; nanodevice; nanoscale; protein function; public health relevance; sperm cell

DESCRIPTION Abstract 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. Public Health Relevance

描述 抽象的 纳米生物技术提供了新形式的医疗的可能性，例如执行生物或机械功能或将药物输送到特定组织的植入式设备。由于蛋白质在如此小的规模下如此有效地发挥作用，它们很可能成为纳米设备的主要组成部分。然而，纳米器件要发挥其潜力，必须克服许多重要的障碍。最关键的问题之一是如何为植入式纳米设备提供能量。我们对哺乳动物精子生理学的研究启发我们制定了解决这一重要问题的策略。精子通过使用通过生殖细胞特异性靶向结构域连接到细胞骨架支持物上的糖酵解酶在整个鞭毛主片中产生 ATP。我们假设通过识别和修饰这些结构域，我们可以生成可以与支持物结合并保留功能的重组糖酵解酶。作为原理证明，我们对该途径中的前两种酶进行了修饰形式，并在与相同支持物偶联时串联显示了它们的活性。据我们所知，这是有机-无机混合装置上多步骤途径中顺序酶活性的首次演示。这些数据也支持我们的假设，即精子提供了如何在纳米设备上本地产生 ATP 的自然模型。我们建议构建其余糖酵解酶的类似修饰重组形式，以及辅酶再生所需的额外酶。然后，我们将在子组件中单独测试这些酶的活性，并在单个支撑物上串联测试这些酶的活性，以努力设计一个系统，通过该系统，可植入纳米装置可以从自由可用的循环葡萄糖中产生自己的能量。如果成功，我们的创新战略将产生一种使能技术，推动纳米生物技术的各种医疗应用。 公共卫生相关性