Department of NanoEngineering , University of California San Diego , La Jolla , California 92093 , United States.
Department of Mechanical Engineering and Materials Science , Duke University , Durham , North Carolina 27708 , United States.
ACS Nano. 2018 Sep 25;12(9):9484-9494. doi: 10.1021/acsnano.8b04817. Epub 2018 Sep 4.
The ability to design and control DNA nanodevices with programmed conformational changes has established a foundation for molecular-scale robotics with applications in nanomanufacturing, drug delivery, and controlling enzymatic reactions. The most commonly used approach for actuating these devices, DNA binding and strand displacement, allows devices to respond to molecules in solution, but this approach is limited to response times of minutes or greater. Recent advances have enabled electrical and magnetic control of DNA structures with sub-second response times, but these methods utilize external components with additional fabrication requirements. Here, we present a simple and broadly applicable actuation method based on the avidity of many weak base-pairing interactions that respond to changes in local ionic conditions to drive large-scale conformational transitions in devices on sub-second time scales. To demonstrate such ion-mediated actuation, we modified a DNA origami hinge with short, weakly complementary single-stranded DNA overhangs, whose hybridization is sensitive to cation concentrations in solution. We triggered conformational changes with several different types of ions including mono-, di-, and trivalent ions and also illustrated the ability to engineer the actuation response with design parameters such as number and length of DNA overhangs and hinge torsional stiffness. We developed a statistical mechanical model that agrees with experimental data, enabling effective interpretation and future design of ion-induced actuation. Single-molecule Förster resonance energy-transfer measurements revealed that closing and opening transitions occur on the millisecond time scale, and these transitions can be repeated with time resolution on the scale of one second. Our results advance capabilities for rapid control of DNA nanodevices, expand the range of triggering mechanisms, and demonstrate DNA nanomachines with tunable analog responses to the local environment.
设计和控制具有编程构象变化的 DNA 纳米器件的能力为分子尺度机器人技术奠定了基础，其应用包括纳米制造、药物输送和控制酶反应。最常用于驱动这些器件的方法是 DNA 结合和链置换，这使得器件能够对溶液中的分子做出响应，但这种方法的响应时间限制在分钟或更长时间。最近的进展使得能够以亚秒级的响应时间进行电和磁控制的 DNA 结构，但这些方法利用具有附加制造要求的外部组件。在这里，我们提出了一种简单且广泛适用的基于许多弱碱基配对相互作用的亲合力的致动方法，该方法响应局部离子条件的变化，以在亚秒级时间尺度上驱动器件的大规模构象转变。为了证明这种离子介导的致动，我们用短的、弱互补单链 DNA 突出端修饰了 DNA 折纸铰链，其杂交对溶液中的阳离子浓度敏感。我们用几种不同类型的离子触发构象变化，包括单价、二价和三价离子，还说明了通过设计参数（例如 DNA 突出端的数量和长度以及铰链扭转刚度）来设计致动响应的能力。我们开发了一个统计力学模型，该模型与实验数据一致，能够有效地解释和设计离子诱导的致动。单分子Förster 共振能量转移测量显示，关闭和打开跃迁发生在毫秒时间尺度上，这些跃迁可以在一秒的时间分辨率内重复。我们的结果提高了快速控制 DNA 纳米器件的能力，扩展了触发机制的范围，并展示了具有可调谐模拟响应的 DNA 纳米机器对局部环境。
