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Nat Nanotechnol. 2010 Nov;5(11):788-91. doi: 10.1038/nnano.2010.212. Epub 2010 Oct 31.

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

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1
Institute for Biophysics, Johannes Kepler University of Linz, A-4040 Linz, Austria.

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.

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PMID:
21037576
PMCID:
PMC3108878
DOI:
10.1038/nnano.2010.212
[Indexed for MEDLINE]
Free PMC Article
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