Single-molecule mechanical fingerprinting with DNA nanoswitch calipers.

Single-molecule mechanical fingerprinting with DNA nanoswitch calipers.
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单分子机械指纹与DNA纳米开关卡尺。

DOI:
10.1038/s41565-021-00979-0
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发表时间:
2021-12
影响因子:
38.3
通讯作者:
Wong WP
Wong WP
中科院分区:
材料科学1区
文献类型:
--
作者:
Shrestha P;Yang D;Tomov TE;MacDonald JI;Ward A;Bergal HT;Krieg E;Cabi S;Luo Y;Nathwani B;Johnson-Buck A;Shih WM;Wong WP

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Decoding the identity of biomolecules from trace samples is a longstanding goal in the field of biotechnology. Advances in DNA analysis have significantly impacted clinical practice and basic research, but corresponding developments for proteins face challenges due to their relative complexity and our inability to amplify them. Despite progress in methods such as mass spectrometry and mass cytometry, single-molecule protein identification remains a highly challenging objective. Toward this end, we combine DNA nanotechnology with single-molecule force spectroscopy to create a mechanically reconfigurable DNA Nanoswitch Caliper (DNC) capable of measuring multiple coordinates on single biomolecules with atomic resolution. Using optical tweezers, we demonstrate absolute distance measurements with angstrom-level precision for both DNA and peptides, and using multiplexed magnetic tweezers, we demonstrate quantification of relative abundance in mixed samples. Measuring distances between DNA-labeled residues, we perform single-molecule fingerprinting of synthetic and natural peptides, and show discrimination, within a heterogeneous population, between different post-translational modifications. DNA Nanoswitch Calipers are a powerful and accessible tool for characterizing distances within nanoscale complexes that will enable new applications in fields such as single-molecule proteomics.
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