Publikation

Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns

Outline:

R. Zhu, S. Howorka, J. Pröll, F. Kienberger, J. Preiner, J. Hesse, A. Ebner, V. Pastushenko, H. Gruber, P. Hinterdorfer - Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns - Nature Nanotechnology, 2010

Abstract:

Atomic force microscopy1 (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 dynamics2–4 of biomolecules by probing the interactions within individual molecules5,6, or between a surface-bound molecule and a cantilever that carries a complementary binding partner7–9. 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.