RNA Nanomotor Based Active Devices for Biology and Medicine

描述（由申请人提供）：纳米技术是真正彻底改变我们的能力，制造和设计的有源器件和系统是小，便宜，超灵敏。生产用于快速和并行检测或健康监测的小型医疗设备的需求正在加剧。此外，随着材料科学和工程的每一个新发展，微制造设备变得越来越小，设计和制造生物启发的纳米级设备和传感器以及驱动这些设备和传感器的超紧凑电源的需求正在出现。大自然可以提供满足上述需求的工具。分子马达，如ATP酶[Noji等人，1997]、细菌鞭毛[Sowa等人，2005]或病毒DNA包装马达[Guo，2002; Shu et al.，2003]可以用来合成纳米级的能量。这些马达中的一些可以产生高达数十或数百皮科牛顿的力。它们中的一些可以使用能量并经由ATP水解产生力，或者使用力并经由电动力或pH梯度以ATP的形式产生能量，效率在80-100%的范围内[Yasuda等人，2001; Aksimentiev等人，2004年]。这些电动机中的一些可以具有100-1000 rpm的旋转速度[Sowa等人，2005年]。近年来，纳米制造能力已经发展到可以在硅晶片上的特定位置生长亚20 nm纳米孔、纳米线和纳米管的程度，使得这些结构可以与生物马达连接，用于诸如纳米机械、过滤、运动以及能量产生和收集的应用。在这个项目中，我们建议开发基于生物纳米马达的主动纳米结构和系统。我们的重点是使用噬菌体phi 29 DNA包装纳米颗粒，其由称为包装RNA或“pRNA”的小RNA分子驱动和调节。这种纳米粒子在将phi 29基因组DNA转运到原衣壳中发挥了新的重要作用。随着在理解这些新系统的结构和机制方面取得更多进展，现在是时候使用基于生物纳米技术的方法来评估这些结构，并使用自上而下和自下而上的制造技术来探索这些纳米马达和合成结构之间的界面，以形成活性纳米结构和纳米系统。我们的核心平台将由pRNA驱动马达组成，该马达通过二维自组装DNA晶体锚定在微加工硅或氧化铝基膜上的纳米多孔膜上。DNA自组装层的使用将确保纳米颗粒的完整性和功能性。这一基本平台的发展和特点本身就是一个重大挑战，需要采取一种协调一致的跨学科办法。我们将在一个混合的硅基设备中集成的nanoparticle和演示其操作，然后整合nanoparticle没有衣壳和演示双链DNA通过电机的易位。一旦完成这些任务，就有可能研究各种技术模块，如微流体通道内的主动泵送表面，主动筛分和过滤，以及与生物学和医学直接相关的许多其他应用。

DESCRIPTION (provided by applicant): Nanotechnology is truly revolutionizing our ability to manufacture and design active devices and systems that are small, cheap, and ultra-sensitive. The need to produce small medical devices for rapid and parallel detection or health monitoring is intensifying. Moreover, as the micro-fabricated devices get smaller and smaller with each new development in materials science and engineering, the need to design and fabricate biologically inspired nanoscale devices and sensors and ultra-compact power sources to drive these devices and sensors are emerging. Nature can provide the tools to address the above needs. Molecular motors, such as ATPase [Noji et al., 1997], bacterial flagellar [Sowa et al., 2005], or viral DNA packaging motors [Guo, 2002; Shu et al., 2003] can be utilized to synthesize power at the nano-scale. Some of these motors can generate force up to tens or hundreds of pico Newtons. Some of them can use energy and generate force, via ATP hydrolysis, or use the force and generate energy in the form of ATP, via electrolocomotive force or pH gradients, with efficiencies in the range of 80-100% [Yasuda et al., 2001; Aksimentiev et al., 2004]. Some of these motors can have rotational speeds of 100-1000 rpm [Sowa et al., 2005]. In the recent years, nanofabrication capabilities have progressed to a point where sub 20nm nanopores, nanowires, and nanotubes can be grown at specific locations on a silicon wafer such that these structures can possibly be interfaced with biological motors for applications such as nanomechanics, filtration, locomotion, and energy generation and harvesting. In this project, we propose to develop active nanostructures and systems based on biological nanomotors. Our focus here would be the use of the bacteriophage phi29 DNA packaging nanomotor that is driven and geared by small RNA molecules termed packaging RNA or "pRNA". This nanomotor has been shown to play a novel and essential role in transporting phi29 genomic DNA into procapsids. As more progress is made in understanding the structure and mechanisms of these novel systems, it is time to evaluate these structures using bionanotechnology-based approaches and to explore the interface between these nanomotors and synthetic structures using top down and bottoms up fabrication technology to form active nanostructures and nanosystems. Our core platform will consist of the pRNA-driving motors anchored on nanoporous membranes on micromachined silicon or Alumina based membrane via a 2-dimensional self- assembled DNA crystal. The use of the DNA self assembled layer will ensure the integrity and functionality of the nanomotor. The development and characterization of this basic platform is a significant challenge in itself and requires a cohesive interdisciplinary approach. We will integrate the nanomotor in a hybrid silicon based device and demonstrate its operation, and then integrate the nanomotor without the capsid and demonstrate the translocation of dsDNA through the motor. Once these tasks are accomplished, it will be possible to investigate various technology modules such as active pumping surfaces within microfluidic channels, active sieving and filtration, and many other applications directly relevant to biology and medicine.