Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns

Rong Zhu, Stefan Howorka, Johannes Pröll, Ferry Kienberger, Johannes Preiner, Jan Hesse, Andreas Ebner, Vassili Ph Pastushenko, Hermann J. Gruber, Peter Hinterdorfer

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Atomic force microscopy (AFM) is a powerful tool for analysing the shapes of individual molecules and the forces acting on them. AFM-based force spectroscopy provides insights into the structural and energetic dynamics of biomolecules by probing the interactions within individual molecules, or between a surface-bound molecule and a cantilever that carries a complementary binding partner. Here, we show that an AFM cantilever with an antibody tether can measure the distances between 5-methylcytidine bases in individual DNA strands with a resolution of 4 Å, thereby revealing the DNA methylation pattern, which has an important role in the epigenetic control of gene expression. The antibody is able to bind two 5-methylcytidine bases of a surface-immobilized DNA strand, and retracting the cantilever results in a unique rupture signature reflecting the spacing between two tagged bases. This nanomechanical approach might also allow related chemical patterns to be retrieved from biopolymers at the single-molecule level.

Original languageEnglish
Pages (from-to)788-791
Number of pages4
JournalNature Nanotechnology
Volume5
Issue number11
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Cytidine/analogs & derivatives
  • DNA Methylation
  • DNA, Single-Stranded/chemistry
  • Epigenesis, Genetic
  • Microscopy, Atomic Force
  • Nanotechnology/methods
  • Nucleic Acid Conformation

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