National Institute of Standards and Technology, Radio Frequency Electronics Group, Boulder CO 325 Broadway St, Boulder, CO, 80305, USA.
School of Molecular Sciences, Arizona State University, 551 E University Dr, Tempe, AZ, 85281, USA.
Nat Commun. 2019 Mar 12;10(1):1174. doi: 10.1038/s41467-019-09017-z.
Detection of conformational changes in biomolecular assemblies provides critical information into biological and self-assembly processes. State-of-the-art in situ biomolecular conformation detection techniques rely on fluorescent labels or protein-specific binding agents to signal conformational changes. Here, we present an on-chip, label-free technique to detect conformational changes in a DNA nanomechanical tweezer structure with microwave microfluidics. We measure the electromagnetic properties of suspended DNA tweezer solutions from 50 kHz to 110 GHz and directly detect two distinct conformations of the structures. We develop a physical model to describe the electrical properties of the tweezers, and correlate model parameters to conformational changes. The strongest indicator for conformational changes in DNA tweezers are the ionic conductivity, while shifts in the magnitude of the cooperative water relaxation indicate the addition of fuel strands used to open the tweezer. Microwave microfluidic detection of conformational changes is a generalizable, non-destructive technique, making it attractive for high-throughput measurements.
生物分子组装体构象变化的检测为生物和自组装过程提供了关键信息。最先进的原位生物分子构象检测技术依赖于荧光标记或蛋白质特异性结合剂来信号构象变化。在这里，我们提出了一种基于微波微流控的无标记芯片技术，用于检测 DNA 纳米机械镊子结构中的构象变化。我们从 50kHz 到 110GHz 测量悬浮 DNA 镊子溶液的电磁特性，并直接检测结构的两种不同构象。我们开发了一个物理模型来描述镊子的电学特性，并将模型参数与构象变化相关联。DNA 镊子构象变化的最强指示是离子电导率，而协同水弛豫幅度的变化则表明添加了用于打开镊子的燃料链。微波微流控检测构象变化是一种可推广的、非破坏性的技术，使其成为高通量测量的理想选择。
