Skip to content
DraconiticResearch
Search Sources API
178,033 studies31 sourcesUpdated 13 min ago
Peer-reviewedCC BY-NCRSC advances

Characterizing the structure of 3D DNA origami in a transmission electron microscope

  • Alyna Ong1
  • Christoph Hadlich2
  • Taekyu Jeong3
  • Darius Pohl1
  • Iman Elbalasy2,4
  • Ralf Seidel2
  • Michael Mertig3,5
  • Bernd Rellinghaus1
5 affiliations
  1. 1Dresden Center for Nanoanalysis (DCN), cfaed, TUD Dresden University of Technology 01062 Dresden Germany
  2. 2Peter-Debye-Institute for Soft Matter Physics, Universität Leipzig 04103 Leipzig Germany
  3. 3Physical Chemistry, TUD Dresden University of Technology 01062 Dresden Germany
  4. 4Faculty of Science, Cairo University 12613 Giza Egypt
  5. 5Kurt-Schwabe-Institut für Mess- und Sensortechnik Meinsberg e.V. 04736 Waldheim Germany
Read full textPDFDOICite

Abstract

DNA origami nanostructures provide programmable control over nanoscale geometry but remain challenging to image due to their low atomic number. Here, we systematically evaluate imaging strategies for both stained and unstained DNA origami deposited on carbon-coated TEM grids. Using Weber contrast as a quantitative metric, we compared different operating modes of (scanning) transmission electron microscopy, (S)TEM, in order to find optimum imaging conditions. STEM was consistently found to deliver the highest contrast, with optimal performance at a camera length of 600 mm towards the high angle annular dark field (HAADF) detector. As expected, the contrast was higher for the thicker three-dimensional nanotubes as compared to DNA 6-helix bundles (6HBs) due to the larger projected thickness of the former. The contrast was effectively enhanced by heavy metal staining with uranyl formate. Notably, 3D molds preserved their designated dimensions upon staining and also largely retained their structural integrity upon complexation with palladium, which also improved the visibility of the structures. These results establish STEM as the optimal approach for high-contrast imaging of DNA origami even of unstained samples and provide practical guidelines for sample preparation and imaging conditions that promote reliable structural visualization.

Related

  1. Automating Nanoparticle Analysis in Transmission Electron Microscopy with Synthetically Trained Segmentation Models
    Natalia Sá, Andrew Stewart
    ChemRxivPreprintCC BYStructural biologyChemRxiv
  2. Crossed laser phase plates for transmission electron microscopy
    Petar N. Petrov, Jessie T. Zhang, Jeremy J. Axelrod +2
    Nature CommunicationsPeer-reviewedCC BYFull text6 citedStructural biologyOpenAlex
  3. Structure of vesicular stomatitis virus L-P-N0 complex by cyro-electron microscopy
    Louis-Marie Bloyet, Sean P. J. Whelan
    Science AdvancesPeer-reviewedCC BY 4.0Full textStructural biologyMicrobiologySci. Adv.CrossrefHALEurope PMC+1
  4. The role of absorption in 3D electron diffraction dynamical structure refinement
    Benjamin Colmey, Tiarnan A.S. Doherty, Shreshth A. Malik +1
    Acta Crystallographica Section A: Foundations and AdvancesPeer-reviewedCC BY 4.0Full textStructural biologyPMC
  5. Cryo-electron microscopy structure of Jabs, a bacteriophage infecting the multidrug-resistant pathogen Mycobacterium abscessus
    C. Cambillau, J. H. Liew, B. S. Y. Tan +3
    bioRxivPreprintCC BY-NC-NDFull textStructural biologyEcologybioRxivHAL

Cite

BibTeXRIS
BibTeX
@article{ong2026characterizing,
  title = {{Characterizing the structure of 3D DNA origami in a transmission electron microscope}},
  author = {Alyna Ong and Christoph Hadlich and Taekyu Jeong and Darius Pohl and Iman Elbalasy and Ralf Seidel and Michael Mertig and Bernd Rellinghaus},
  journal = {RSC advances},
  year = {2026},
  month = oct,
  doi = {10.1039/d6ra01070a},
  url = {https://europepmc.org/article/PMC/PMC13669860},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Characterizing the structure of 3D DNA origami in a transmission electron microscope
AU  - Alyna Ong
AU  - Christoph Hadlich
AU  - Taekyu Jeong
AU  - Darius Pohl
AU  - Iman Elbalasy
AU  - Ralf Seidel
AU  - Michael Mertig
AU  - Bernd Rellinghaus
PY  - 2026
DA  - 2026/10/15
JO  - RSC advances
DO  - 10.1039/d6ra01070a
UR  - https://europepmc.org/article/PMC/PMC13669860
AB  - DNA origami nanostructures provide programmable control over nanoscale geometry but remain challenging to image due to their low atomic number. Here, we systematically evaluate imaging strategies for both stained and unstained DNA origami deposited on carbon-coated TEM grids. Using Weber contrast as a quantitative metric, we compared different operating modes of (scanning) transmission electron microscopy, (S)TEM, in order to find optimum imaging conditions. STEM was consistently found to deliver the highest contrast, with optimal performance at a camera length of 600 mm towards the high angle annular dark field (HAADF) detector. As expected, the contrast was higher for the thicker three-dimensional nanotubes as compared to DNA 6-helix bundles (6HBs) due to the larger projected thickness of the former. The contrast was effectively enhanced by heavy metal staining with uranyl formate. Notably, 3D molds preserved their designated dimensions upon staining and also largely retained their structural integrity upon complexation with palladium, which also improved the visibility of the structures. These results establish STEM as the optimal approach for high-contrast imaging of DNA origami even of unstained samples and provide practical guidelines for sample preparation and imaging conditions that promote reliable structural visualization.
SN  - 2046-2069
ER  -