Superresolution intrinsic fluorescence imaging of chromatin utilizing native, unmodified nucleic acids for contrast

Biqin Dong, Luay M. Almassalha, Yolanda Stypula-Cyru, Ben E. Urban, John E. Chandler, The Quyen Nguyen, Cheng Sun, Hao F. Zhang*, Vadim Backman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Visualizing the nanoscale intracellular structures formed by nucleic acids, such as chromatin, in nonperturbed, structurally and dynamically complex cellular systems, will help expand our understanding of biological processes and open the next frontier for biological discovery. Traditional superresolution techniques to visualize subdiffractional macromolecular structures formed by nucleic acids require exogenous labels that may perturb cell function and change the very molecular processes they intend to study, especially at the extremely high label densities required for superresolution. However, despite tremendous interest and demonstrated need, label-free optical superresolution imaging of nucleotide topology under native nonperturbing conditions has never been possible. Here we investigate a photoswitching process of native nucleotides and present the demonstration of subdiffraction-resolution imaging of cellular structures using intrinsic contrast from unmodified DNA based on the principle of single-molecule photon localization microscopy (PLM). Using DNA-PLM, we achieved nanoscopic imaging of interphase nuclei and mitotic chromosomes, allowing a quantitative analysis of the DNA occupancy level and a subdiffractional analysis of the chromosomal organization. This study may pave a new way for label-free superresolution nanoscopic imaging of macromolecular structures with nucleotide topologies and could contribute to the development of new DNA-based contrast agents for superresolution imaging.

Original languageEnglish (US)
Pages (from-to)9716-9721
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
StatePublished - Aug 30 2016


  • Chromatin topology
  • Chromosome
  • Label-free imaging
  • Nucleic acids
  • Superresolution fluorescence microscopy

ASJC Scopus subject areas

  • General


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