Experimental Biophysics & Applied Nanoscience, Faculty of Physics, Bielefeld University, 33615, Bielefeld, Germany.
Lehrstuhl für Anorganische Chemie I, Faculty of Chemistry, Bielefeld University, 33615, Bielefeld, Germany.
J Nanobiotechnology. 2023 Jan 23;21(1):26. doi: 10.1186/s12951-023-01784-8.
Dinuclear copper complexes have been designed for molecular recognition in order to selectively bind to two neighboring phosphate moieties in the backbone of double strand DNA. Associated biophysical, biochemical and cytotoxic effects on DNA were investigated in previous works, where atomic force microscopy (AFM) in ambient conditions turned out to be a particular valuable asset, since the complexes influence the macromechanical properties and configurations of the strands. To investigate and scrutinize these effects in more depth from a structural point of view, cutting-edge preparation methods and scanning force microscopy under ultra-high vacuum (UHV) conditions were employed to yield submolecular resolution images. DNA strand mechanics and interactions could be resolved on the single base pair level, including the amplified formation of melting bubbles. Even the interaction of singular complex molecules could be observed. To better assess the results, the appearance of treated DNA is also compared to the behavior of untreated DNA in UHV on different substrates. Finally, we present data from a statistical simulation reasoning about the nanomechanics of strand dissociation. This sort of quantitative experimental insights paralleled by statistical simulations impressively shade light on the rationale for strand dissociations of this novel DNA interaction process, that is an important nanomechanistic key and novel approach for the development of new chemotherapeutic agents.
双核铜配合物被设计用于分子识别,以选择性地结合双链 DNA 骨架中两个相邻的磷酸部分。在以前的工作中,研究了与之相关的生物物理、生化和细胞毒性对 DNA 的影响,其中原子力显微镜(AFM)在环境条件下成为一个特别有价值的工具,因为这些配合物会影响链的宏观机械性能和构型。为了从结构角度更深入地研究和仔细观察这些影响,采用了尖端的制备方法和超高真空(UHV)条件下的扫描力显微镜,以获得亚分子分辨率的图像。DNA 链的力学和相互作用可以在单个碱基对水平上得到解析,包括放大的熔解泡的形成。甚至可以观察到单个配合物分子的相互作用。为了更好地评估结果,还将处理过的 DNA 的外观与未经处理的 DNA 在不同基底上的 UHV 行为进行了比较。最后,我们从统计模拟中呈现了有关链解离纳米力学的数据,这些定量实验见解与统计模拟一起,令人印象深刻地阐明了这种新型 DNA 相互作用过程中链解离的基本原理,这是开发新型化疗药物的重要纳米力学关键和新方法。