Nanoscale energy production for implantable medical devices

描述 摘要 纳米生物技术提供了新形式的医学治疗的可能性，例如执行生物或机械功能的可植入装置，或将药物递送到特定组织。由于蛋白质在这种小规模下的功能如此有效，它们可能会成为纳米器件的主要组成部分。然而，一些重要的障碍，必须克服纳米器件实现其潜力。最关键的问题之一是如何为可植入的纳米器件提供能量。我们对哺乳动物精子生理学的研究启发了我们解决这一重要问题的策略。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支持物上，在整个鞭毛主要部分产生ATP。我们假设，通过鉴定和修饰这些结构域，我们可以产生重组糖酵解酶，可以结合到一个支持和保留功能。作为原理的证明，我们已经对该途径中的前两种酶进行了修饰，并在与相同的载体偶联时显示了它们的活性。据我们所知，这是第一次证明在一个混合的有机-无机设备上的多步途径中的顺序酶活性。这些数据也支持了我们的假设，即精子提供了一个天然的模型，说明如何在纳米器件上局部产生ATP。我们建议构建类似的糖酵解酶的其余部分的重组形式，以及辅酶再生所需的额外的酶。然后，我们将单独测试这些酶的活性，在子组件中，并在我们的努力设计一个系统，通过该系统，可植入的纳米器件可以从自由获得的循环葡萄糖中产生自己的能量。如果成功的话，我们的创新战略将产生一种使能技术，该技术将推动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