Nanoscale energy production for implantable medical devices

纳米生物技术提供了新的医疗形式的可能性，例如可植入的设备 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 因此，在如此小的规模下，它们很可能是纳米设备的主要组成部分。然而，一些人 必须克服重要的障碍，才能使纳米设备实现其潜力。最关键的问题之一 问题是如何为可植入的纳米设备提供能量。我们在哺乳动物生理学方面的工作 精子激发了我们解决这一重要问题的战略。精子在整个过程中产生三磷酸腺苷 利用糖酵解酶通过生殖细胞特异性连接到细胞骨架支架上的鞭毛主体片段 目标域。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一种载体上并保留功能。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，并在以下情况下连续显示了它们的活性 再加上同样的支撑。据我们所知，这是第一次展示顺序酶 有机-无机混合器件上多步骤途径的活性。这些数据也支持我们的假设 这种精子为如何在纳米设备上本地生产ATP提供了一个自然模型。 我们建议构建糖酵解的其余酶的类似修改的重组形式，如 以及辅酶再生所需的额外酶。然后我们将测试这些活动 在我们的努力中，这些酶单独地，在子组件中，并在单个载体上串联 一种可植入的纳米设备可以从自由循环中产生自身能量的系统 葡萄糖。如果成功，我们的创新战略将产生一种使能技术，应该会推动 纳米生物技术的各种医疗应用。

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.