Skip to main content
SpringerLink
Log in

The dynamic interactions between chemotherapy drugs and plasmid DNA investigated by atomic force microscopy

基于AFM的化疗药物与质粒DNA间动态相互作用观测

  • Articles
  • Published:
Science China Materials Aims and scope Submit manuscript

Abstract

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.

摘要

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61: 69–90

    Article  Google Scholar 

  2. DeVita VT, Rosenberg SA. Two hundred years of cancer research. N Engl J Med, 2012, 366: 2207–2214

    Article  Google Scholar 

  3. Nars MS, Kaneno R. Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy. Int J Cancer, 2013, 132: 2471–2478

    Article  Google Scholar 

  4. Nitiss JL. Targeting DN Atopoisomerase II in cancer chemotherapy. Nat Rev Cancer, 2009, 9: 338–350

    Article  Google Scholar 

  5. Dupres V, Alsteens D, Andre G, et al. Fishing single molecules on live cells. Nano Today, 2009, 4: 262–268

    Article  Google Scholar 

  6. Lyubchenko YL, Shlyakhtenko LS, Ando T. Imaging of nucleic acids with atomic force microscopy. Methods, 2011, 54: 274–283

    Article  Google Scholar 

  7. Ido S, Kimiya H, Kobayashi K, et al. Immunoactive two-dimensional self-assembly of monoclonal antibodies in aqueous solution revealed by atomic forcemicroscopy. NatMater, 2014, 13: 264–270

    Google Scholar 

  8. Chiaruttini N, Redondo-Morata L, Colom A, et al. Relaxation of loaded ESCRT-III spiral springs drives membrane deformation. Cell, 2015, 163: 866–879

    Article  Google Scholar 

  9. Alonso-Sarduy L, Longo G, Dietler G, et al. Time-lapse AFM imaging of DNA conformational changes induced by daunorubicin. Nano Lett, 2013, 13: 5679–5684

    Article  Google Scholar 

  10. Krautbauer R, Clausen-Schaumann H, Gaub HE. Cisplatin changes the mechanics of single DNA molecules. Angew Chem Int Ed, 2000, 39: 3912–3915

    Article  Google Scholar 

  11. Liu N, Bu T, Song Y, et al. The nature of the force-induced conformation transition of dsDNA studied by using singlemolecule force spectroscopy. Langmuir, 2010, 26: 9491–9496

    Article  Google Scholar 

  12. Kodera N, Yamamoto D, Ishikawa R, et al. Video imaging of walkingmyosin V by high-speed atomic forcemicroscopy. Nature, 2010, 468: 72–76

    Article  Google Scholar 

  13. Kalle W, Strappe P. Atomic force microscopy on chromosomes, chromatin and DNA: a review. Micron, 2012, 43: 1224–1231

    Article  Google Scholar 

  14. Pyne A, Thompson R, Leung C, et al. Single-molecule reconstruction of oligonucleotide secondary structure by atomic force microscopy. Small, 2014, 10: 3257–3261

    Article  Google Scholar 

  15. Li M, Liu L, Xi N, et al. Progress in measuring biophysical properties of membrane proteins with AFM single-molecule force spectroscopy. Chin Sci Bull, 2014, 59: 2717–2725

    Article  Google Scholar 

  16. Li M, Xiao X, Liu L, et al. Rapid recognition and functional analysis of membrane proteins on human cancer cells using atomic force microscopy. J Immunological Methods, 2016, 436: 41–49

    Article  Google Scholar 

  17. Wiggins PA, van der Heijden T, Moreno-Herrero F, et al. High flexibility of DNA on short length scales probed by atomic force microscopy. Nat Nanotech, 2006, 1: 137–141

    Article  Google Scholar 

  18. Podesta A, Imperadori L, Colnaghi W, et al. Atomic force microscopy study of DNA deposited on poly l-ornithine-coatedmica. J Microsc, 2004, 215: 236–240

    Article  Google Scholar 

  19. Hou XM, Zhang XH, Wei KJ, et al. Cisplatin induces loop structures and condensation of single DNA molecules. Nucleic Acids Res, 2009, 37: 1400–1410

    Article  Google Scholar 

  20. Liu Z, Tan S, Zu Y, et al. The interactions of cisplatin and DNA studied by atomic force microscopy. Micron, 2010, 41: 833–839

    Article  Google Scholar 

  21. Nuttall P, Lee K, Ciccarella P, et al. Single-molecule studies of unlabeled full-length p53 protein binding to DNA. J Phys Chem B, 2016, 120: 2106–2114

    Article  Google Scholar 

  22. Cassina V, Manghi M, Salerno D, et al. Effects of cytosine methylation on DNA morphology: an atomic force microscopy study. BBA—Gen Subjects, 2016, 1860: 1–7

    Article  Google Scholar 

  23. Cassina V, Seruggia D, Beretta GL, et al. Atomic force microscopy study of DNA conformation in the presence of drugs. Eur Biophys J, 2011, 40: 59–68

    Article  Google Scholar 

  24. Cesconetto EC, Junior FSA, Crisafuli FAP, et al. DNA interaction with Actinomycin D: mechanical measurements reveal the details of the binding data. Phys Chem Chem Phys, 2013, 15: 11070–11077

    Article  Google Scholar 

  25. Rafique B, Khalid AM, Akhtar K, et al. Interaction of anticancer drug methotrexate with DNA analyzed by electrochemical and spectroscopic methods. Biosens Bioelectron, 2013, 44: 21–26

    Article  Google Scholar 

  26. Heng JB, Aksimentiev A, Ho C, et al. The electromechanics ofDNA in a synthetic nanopore. Biophys J, 2006, 90: 1098–1106

    Article  Google Scholar 

  27. Liu Z, Li Z, Zhou H, et al. Imaging DNA molecules onmica surface by atomic force microscopy in air and in liquid. Microsc Res Tech, 2005, 66: 179–185

    Article  Google Scholar 

  28. Sun L, Zhao D, Zhang Y, et al. DNA adsorption and desorption on mica surface studied by atomic forcemicroscopy. Appl Surface Sci, 2011, 257: 6560–6567

    Article  Google Scholar 

  29. Miyagi A, Ando T, Lyubchenko YL. Dynamics of nucleosomes assessed with time-lapse high-speed atomic force microscopy. Biochemistry, 2011, 50: 7901–7908

    Article  Google Scholar 

  30. Ficarra E, Masotti D, Macii E, et al. Automatic intrinsic DNA curvature computation from AFM images. IEEE Trans Biomed Eng, 2005, 52: 2074–2086

    Article  Google Scholar 

  31. Thomson NH, Santos S, Mitchenall LA, et al. DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases. Sci Rep, 2014, 4: 6158

    Article  Google Scholar 

  32. Jo K, Dhingra DM, Odijk T, et al. A single-molecule barcoding system using nanoslits for DNA analysis. Proc Natl Acad Sci USA, 2007, 104: 2673–2678

    Article  Google Scholar 

  33. Brinkers S, Dietrich HRC, de Groote FH, et al. The persistence length of double stranded DNA determined using dark field tethered particle motion. J Chem Phys, 2009, 130: 215105–215105

    Article  Google Scholar 

  34. Brunet A, Tardin C, Salomé L, et al. Dependence of DNA persistence length on ionic strength of solutions with monovalent and divalent salts: a joint theory–experiment study. Macromolecules, 2015, 48: 3641–3652

    Article  Google Scholar 

  35. Geggier S, Kotlyar A, Vologodskii A. Temperature dependence of DNA persistence length. Nucleic Acids Res, 2011, 39: 1419–1426

    Article  Google Scholar 

  36. Canetta E, Riches A, Borger E, et al. Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy. Acta Biomater, 2014, 10: 2043–2055

    Article  Google Scholar 

  37. Linko V, Ora A, Kostiainen MA. DNA nanostructures as smart drug-delivery vehicles and molecular devices. Trends Biotech, 2015, 33: 586–594

    Article  Google Scholar 

  38. Wu N, Willner I. pH-stimulated reconfiguration and structural isomerization of origami dimer and trimer systems. Nano Lett, 2016, 16: 6650–6655

    Article  Google Scholar 

  39. van Loenhout MTJ, de Grunt MV, Dekker C. Dynamics of DNA supercoils. Science, 2012, 338: 94–97

    Article  Google Scholar 

  40. Oberstrass FC, Fernandes LE, Bryant Z. Torque measurements reveal sequence-specific cooperative transitions in supercoiled DNA. Proc Natl Acad Sci USA, 2012, 109: 6106–6111

    Article  Google Scholar 

  41. Pontinha ADR, Jorge SMA, Chiorcea Paquim AM, et al. In situ evaluation of anticancer drug methotrexate–DNA interaction using a DNA-electrochemical biosensor and AFM characterization. Phys Chem Chem Phys, 2011, 13: 5227–5234

    Article  Google Scholar 

  42. Dasari S, Bernard Tchounwou P. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacology, 2014, 740: 364–378

    Article  Google Scholar 

  43. Li M, Liu LQ, Xi N, et al. Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy. Sci China Life Sci, 2015, 58: 889–901

    Article  Google Scholar 

  44. Li M, Xiao X, Liu L, et al. Nanoscale quantifying the effects of targeted drug on chemotherapy in lymphoma treatment using atomic force microscopy. IEEE Trans Biomed Eng, 2016, 63: 2187–2199

    Article  Google Scholar 

  45. Ando T, Uchihashi T, Scheuring S. Filming biomolecular processes by high-speed atomic force microscopy. Chem Rev, 2014, 114: 3120–3188

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (61503372, 61522312, 61327014 and 61433017), the Youth Innovation Promotion Association CAS, and the CAS FEA International Partnership Program for Creative Research Teams.

Author information

Authors and Affiliations

  1. State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110016, China

    Mi Li  (李密), Lianqing Liu  (刘连庆), Ning Xi  (席宁) & Yuechao Wang  (王越超)

  2. Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing, 100071, China

    Xiubin Xiao  (肖秀斌)

  3. Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, 48824, USA

    Ning Xi  (席宁)

Authors
  1. Mi Li  (李密)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lianqing Liu  (刘连庆)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiubin Xiao  (肖秀斌)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ning Xi  (席宁)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuechao Wang  (王越超)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lianqing Liu  (刘连庆) or Ning Xi  (席宁).

Additional information

Mi Li is currently an associate professor at the State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China. His research interests include AFM-based imaging and mechanical analysis of biological systems.

Lianqing Liu is currently a professor at the State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China. His research interests include micro/nano system, nanodevice fabrication, nanobiotechnology and biosensors.

Ning Xi is currently a John D. Ryder Professor of Electrical and Computer Engineering at Michigan State University, East Lansing and a professor of Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China. His research interests include robotics, manufacturing automation, nanosensors, micro/nanomanufacturing, and intelligent control and systems.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Liu, L., Xiao, X. et al. The dynamic interactions between chemotherapy drugs and plasmid DNA investigated by atomic force microscopy. Sci. China Mater. 60, 269–278 (2017). https://doi.org/10.1007/s40843-016-5152-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40843-016-5152-2

Keywords

Search

Navigation