摘要
The advent of atomic force microscopy （AFM） provides a powerful tool for imaging individual DNA molecules. Chemotherapy drugs are often related to DNAs. Though many specific drug-DNA interactions have been observed by AFM, knowledge about the dynamic interactions between chemotherapy drugs and plasmid DNAs is still scarce. In this work, AFM was applied to investigate the nanoscale interactions between plasmid DNAs and two commercial chemotherapy drugs （methotrexate and cisplatin）. Plasmid DNAs were immobilized on mica which was coated by silanes in advance. AFM imaging distinctly revealed the dynamic changes of single plasmid DNAs after the stimulation of methotrexate and cisplatin. Geometric features of plasmid DNAs were extracted from AFM images and the statistical results showed that the geometric features of plasmid DNAs changed significantly after the stimulation of drugs. This research provides a novel idea to study the actions of chemotherapy drugs against plasmid DNAs at the single-molecule level.
原子力显微镜(atomic forcemicroscopy,AFM)的出现为单根DNA分子形貌成像提供了新的技术手段.DNA是许多化疗药物的作用靶点.尽管研究人员利用AFM对化疗药物与DNA之间的相互作用进行了大量研究,但对于化疗药物与质粒DNA间动态相互作用过程的认知还很缺乏.本文利用AFM研究了纳米尺度下质粒DNA与两种商用化疗药物(甲氨蝶呤,顺铂)之间的相互作用.质粒DNA吸附在硅烷化的云母表面.AFM成像结果清晰地揭示出化疗药物刺激下单根质粒DNA形貌的动态变化.从AFM图像中提取出质粒DNA的几何特征,统计结果表明化疗药物刺激后质粒DNA的几何特征发生了显著变化.本研究为单分子尺度下研究化疗药物与质粒DNA之间的相互作用提供了新的思路.
基金
supported by the National Natural Science Foundation of China (61503372, 61522312, 61327014 and 61433017)
the Youth Innovation Promotion Association CAS
the CAS FEA International Partnership Program for Creative Research Teams
