Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns

被引：54

作者：

Zhu, Rong ^{[1
,2
]}

Howorka, Stefan ^{[3
,4
]}

Proell, Johannes ^{[5
]}

Kienberger, Ferry ^{[1
]}

Preiner, Johannes ^{[1
]}

Hesse, Jan ^{[1
,3
]}

Ebner, Andreas ^{[1
]}

Pastushenko, Vassili Ph. ^{[1
]}

Gruber, Hermann J. ^{[1
]}

Hinterdorfer, Peter ^{[1
,2
,3
]}

机构：

[1] Johannes Kepler Univ Linz, Inst Biophys, A-4040 Linz, Austria

[2] Johannes Kepler Univ Linz, Christian Doppler Lab Nanoscop Methods Biophys, A-4040 Linz, Austria

[3] Ctr Adv Bioanal GmbH, A-4020 Linz, Austria

[4] UCL, Dept Chem, London WC1H 0AJ, England

[5] Elisabethinen Hosp, Dept Internal Med 1, A-4010 Linz, Austria

来源：

NATURE NANOTECHNOLOGY | 2010年 / 5卷 / 11期

基金：

奥地利科学基金会;

关键词：

ATOMIC-FORCE MICROSCOPY; SINGLE-MOLECULE; OLIGONUCLEOTIDE MICROARRAYS; COMPLEMENTARY STRANDS; REAL-TIME; SPECTROSCOPY; ANTIBODIES; 5-METHYLCYTOSINE; POLYMERASE; PROTEIN;

D O I：

10.1038/nnano.2010.212

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Atomic force microscopy(1) (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(2-4) of biomolecules by probing the interactions within individual molecules(5,6), or between a surface-bound molecule and a cantilever that carries a complementary binding partner(7-9). 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 angstrom, 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.

引用

页码：788 / 791

页数：4

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