Visualization of unstained DNA nanostructures with advanced in-focus phase contrast TEM techniques
Yoones Kabiri (Kavli institute of nanoscience Delft, TU Delft - BN/Cees Dekker Lab)
Raimond B.G. Ravelli (Maastricht University)
Tibor Lehnert (University of Ulm)
Haoyuan Qi (University of Ulm)
Allard J. Katan (TU Delft - QN/Afdelingsbureau, Kavli institute of nanoscience Delft)
Natascha Roest (Maastricht University)
Ute Kaiser (University of Ulm)
Cees Dekker (TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)
Peter J. Peters (Maastricht University)
Henny Zandbergen (Kavli institute of nanoscience Delft, TU Delft - QN/Zandbergen Lab)
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Abstract
Over the last few years, tremendous progress has been made in visualizing biologically important macromolecules using transmission electron microscopy (TEM) and understanding their structure-function relation. Yet, despite the importance of DNA in all forms of life, TEM visualization of individual DNA molecules in its native unlabeled form has remained extremely challenging. Here, we present high-contrast images of unstained single-layer DNA nanostructures that were obtained using advanced in-focus phase contrast TEM techniques. These include sub-Ångstrom low voltage electron microscopy (SALVE), the use of a volta-potential phase plate (VPP), and dark-field (DF) microscopy. We discuss the advantages and drawbacks of these techniques for broad applications in structural biology and materials science.