Abstract

DNA covers the genetic information in all living organisms. Numerous intrinsic and extrinsic factors may influence the local structure of the DNA molecule or compromise its integrity. Detailed understanding of structural modifications of DNA resulting from interactions with other molecules and surrounding environment is of central importance for the future development of medicine and pharmacology. In this paper, we review the recent achievements in research on DNA structure at nanoscale. In particular, we focused on the molecular structure of DNA revealed by high-resolution AFM (Atomic Force Microscopy) imaging at liquid/solid interfaces. Such detailed structural studies were driven by the technical developments made in SPM (Scanning Probe Microscopy) techniques. Therefore, we describe here the working principles of AFM modes allowing high-resolution visualization of DNA structure under native (liquid) environment. While AFM provides well-resolved structure of molecules at nanoscale, it does not reveal the chemical structure and composition of studied samples. The simultaneous information combining the structural and chemical details of studied analyte allows achieve a comprehensive picture of investigated phenomenon. Therefore, we also summarize recent molecular spectroscopy studies, including Tip-Enhanced Raman Spectroscopy (TERS), on the DNA structure and its structural rearrangements.

Highlights

  • The DNA molecule is one of the most interesting objects to scientists due to its biological significance and properties determined by the unique chemical composition and dynamic structure

  • Heenan and Perkins [18] reported on the protocol of DNA fixation on mica well suited for AFM imaging in liquids without the loss of physiologically relevant information

  • The Tip-Enhanced Raman Spectroscopy (TERS) findings obtained in liquid for amyloid-β showing the rearmament of secondary structure from protofibrils to fibrils conversion in the aggregation process, already proved the great potential of this technique applied in liquid environment in the research on structural transitions of biomolecules [107]

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Summary

Introduction

The DNA molecule is one of the most interesting objects to scientists due to its biological significance and properties determined by the unique chemical composition and dynamic structure. Measurements undertaken in liquids open the new possibilities of monitoring structural rearrangements that occur in biomolecules upon biologically significant processes such as interactions between DNA and other macromolecules like proteins or peptides as well as chemical agents including drugs. SPM provides nanometric spatial resolution; the molecular information that can be achieved is still limited This manuscript presents a view on combination of SPM with molecular spectroscopic techniques as an important future scientific direction, which will play an important role in exploration of DNA local molecular dynamics and its role in inter and intramolecular interactions

Preparation of DNA Samples for High-Resolution AFM Imaging
Dynamic AFM Modes
AM-AFM Imaging
PeakForce Tapping
FM-AFM Imaging
AFM Profiling of DNA
Revealing Submolecular Structure of Individual DNA Molecules
SERS and TERS Research on DNA Structure
Protective Role of Solvents
Concluding Remarks and Future Outlook
Full Text
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