Single molecule force spectroscopy is a powerful approach to probe the structure, conformational changes, and kinetic properties of biological and synthetic macromolecules. However, common approaches to apply forces to biomolecules require expensive and cumbersome equipment and relatively large probes such as beads or cantilevers, which limits their use for many environments and makes integrating with other methods challenging. Furthermore, existing methods have key limitations such as an inability to apply compressive forces on single molecules. We report a nanoscale DNA force spectrometer (nDFS), which is based on a DNA origami hinge with tunable mechanical and dynamic properties. The angular free energy landscape of the nDFS can be engineered across a wide range through substitution of less than 5% of the strand components. We further incorporate a removable strut that enables reversible toggling of the nDFS between open and closed states to allow for actuated application of tensile and compressive forces. We demonstrate the ability to apply compressive forces by inducing a large bend in a 249bp DNA molecule, and tensile forces by inducing DNA unwrapping of a nucleosome sample. These results establish a versatile tool for force spectroscopy and robust methods for designing nanoscale mechanical devices with tunable force application.

中文翻译：

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能够对生物分子施加张力和压力的纳米级 DNA 力谱仪

单分子力谱是探测生物和合成大分子的结构、构象变化和动力学特性的有效方法。然而，向生物分子施加力的常见方法需要昂贵且笨重的设备以及相对较大的探针（例如珠子或悬臂），这限制了它们在许多环境中的使用，并且使得与其他方法的集成具有挑战性。此外，现有方法具有关键局限性，例如无法对单个分子施加压缩力。我们报告了一种纳米级 DNA 力谱仪 (nDFS)，它基于具有可调机械和动态特性的 DNA 折纸铰链。nDFS 的角度自由能景观可以通过替换少于 5% 的线组件来在很宽的范围内进行设计。我们进一步采用了一个可拆卸的支柱，使 nDFS 在打开和关闭状态之间可逆切换，以允许拉力和压力的驱动应用。我们展示了通过在 249bp DNA 分子中诱导大弯曲来施加压缩力的能力，以及通过诱导核小体样本的 DNA 解包来施加张力的能力。这些结果建立了力谱的多功能工具和用于设计具有可调力应用的纳米级机械装置的稳健方法。