Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns
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
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.