Nanoscale energy production for implantable medical devices

描述 摘要 纳米生物技术提供了新的医疗形式的可能性，例如执行生物或机械功能的可植入设备，或将药物输送到特定组织。由于蛋白质在如此小的规模下发挥着如此高效的功能，它们很可能成为纳米设备的主要组成部分。然而，要实现纳米器件的潜力，必须克服一些重要的障碍。最关键的问题之一是如何为可植入的纳米设备提供能量。我们在哺乳动物精子生理学方面的工作启发了我们解决这一重要问题的战略。精子利用糖酵解酶通过生殖细胞特异性靶向结构域连接到细胞骨架上，从而在鞭毛主体部分产生ATP。我们假设，通过识别和修饰这些结构域，我们可以产生能够与载体结合并保留功能的重组糖酵解酶。作为原理的证明，我们已经对这一途径中的前两种酶进行了修饰，并显示了当连接到相同的载体上时，它们的系列活性。据我们所知，这是第一次在有机-无机混合设备上的多步骤途径中展示连续的酶活性。这些数据还支持我们的假设，即精子为如何在纳米设备上本地产生ATP提供了一个自然模型。我们建议构建糖酵解其余酶的类似修改的重组形式，以及辅酶再生所需的额外酶。然后，我们将分别测试这些酶的活性，在组件中，并在单个载体上串联测试，以努力设计一种系统，通过该系统，可植入的纳米设备可以从可自由获得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，应该会促进纳米生物技术的各种医疗应用。 公共卫生相关性

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