Tuning the Sensitivity of MoS2 Nanopores: From Labeling to Labeling-Free Detection of DNA Methylation
Chunxiao Zhao
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorYibo Yang
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorPinlong Zhao
School of Cyberspace, Hangzhou Dianzi University, Hangzhou, 310018 P. R. China
Search for more papers by this authorChongbin Shi
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorTianhui Tan
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorCorresponding Author
Hongzhen Bai
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Jiandong Feng
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorChunxiao Zhao
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorYibo Yang
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorPinlong Zhao
School of Cyberspace, Hangzhou Dianzi University, Hangzhou, 310018 P. R. China
Search for more papers by this authorChongbin Shi
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorTianhui Tan
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
Search for more papers by this authorCorresponding Author
Hongzhen Bai
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Jiandong Feng
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, Hangzhou, 310058 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
DNA methylation discrimination is often challenged by complicated pretreatment, insufficient sensitivity, and suboptimal accuracy. Here, single-molecule readout of DNA methylation is reported using single-layer MoS2 nanopores. By tuning pore dimension, the sensitivity of MoS2 nanopores is manipulated, empowering both labeling and labeling-free strategies for DNA methylation discrimination. With methyl-CpG-binding domain protein 1 (MBD1)-labeled methylated DNA translocation in customized nanopores, multiple methylated sites with distance as short as 70 bp in double strand DNA can be resolved. To further improve spatial resolution, small MoS2 nanopores are engineered with single-nucleotide sensitivity, realizing labeling-free methylation detection with single-nucleotide resolution to recognize two nucleotides with only one methyl difference. This study demonstrates the availability of engineered MoS2 nanopores in DNA methylation detection, underscoring their potential for epigenetic alteration research at the single-molecule level.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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References
- 1I. Keshet, J. Yisraeli, H. Cedar, Proc. Natl. Acad. Sci. USA 1985, 82, 2560.
- 2H. Cedar, Cell 1988, 53, 3.
- 3A. Razin, H. Cedar, Microbiol. Rev. 1991, 55, 451.
- 4A. Bird, Cell 1992, 70, 5.
- 5H. Wu, Y. Zhang, Cell 2014, 156, 45.
- 6M. Frommer, L. E. McDonald, D. S. Millar, C. M. Collis, F. Watt, G. W. Grigg, P. L. Molloy, C. L. Paul, Proc. Natl. Acad. Sci. USA 1992, 89, 1827.
- 7K. Tanaka, A. Okamoto, Bioorg. Med. Chem. Lett. 2007, 17, 1912.
- 8Y. Liu, Z. Hu, J. Cheng, P. Siejka-Zielińska, J. Chen, M. Inoue, A. A. Ahmed, C.-X. Song, Nat. Commun. 2021, 12, 618.
- 9E. K. Schutsky, J. E. DeNizio, P. Hu, M. Y. Liu, C. S. Nabel, E. B. Fabyanic, Y. Hwang, F. D. Bushman, H. Wu, R. M. Kohli, Nat. Biotechnol. 2018, 36, 1083.
- 10J. Eid, A. Fehr, J. Gray, K. Luong, J. Lyle, G. Otto, P. Peluso, D. Rank, P. Baybayan, B. Bettman, A. Bibillo, K. Bjornson, B. Chaudhuri, F. Christians, R. Cicero, S. Clark, R. Dalal, A. deWinter, J. Dixon, M. Foquet, A. Gaertner, P. Hardenbol, C. Heiner, K. Hester, D. Holden, G. Kearns, X. Kong, R. Kuse, Y. Lacroix, S. Lin, et al., Science 2009, 323, 133.
- 11B. A. Flusberg, D. R. Webster, J. H. Lee, K. J. Travers, E. C. Olivares, T. A. Clark, J. Korlach, S. W. Turner, Nat. Methods 2010, 7, 461.
- 12S. Ardui, A. Ameur, J. R. Vermeesch, M. S. Hestand, Nucleic Acids Res. 2018, 46, 2159.
- 13K. Lee, K.-B. Park, H.-J. Kim, J.-S. Yu, H. Chae, H.-M. Kim, K.-B. Kim, Adv. Mater. 2018, 30, 1704680.
- 14Y.-L. Ying, Z.-L. Hu, S. Zhang, Y. Qing, A. Fragasso, G. Maglia, A. Meller, H. Bayley, C. Dekker, Y.-T. Long, Nat. Nanotechnol. 2022, 17, 1136.
- 15N. Meyer, J. Torrent, S. Balme, Small Methods 2024, https://doi.org/10.1002/smtd.202400058.
- 16E. A. Manrao, I. M. Derrington, M. Pavlenok, M. Niederweis, J. H. Gundlach, PLoS One 2011, 6, e25723.
- 17A. H. Laszlo, I. M. Derrington, H. Brinkerhoff, K. W. Langford, I. C. Nova, J. M. Samson, J. J. Bartlett, M. Pavlenok, J. H. Gundlach, Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 18904.
- 18J. Schreiber, Z. L. Wescoe, R. Abu-Shumays, J. T. Vivian, B. Baatar, K. Karplus, M. Akeson, Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 18910.
- 19Y. Wang, S. Zhang, W. Jia, P. Fan, L. Wang, X. Li, J. Chen, Z. Cao, X. Du, Y. Liu, K. Wang, C. Hu, J. Zhang, J. Hu, P. Zhang, H.-Y. Chen, S. Huang, Nat. Nanotechnol. 2022, 17, 976.
- 20J. Clarke, H.-C. Wu, L. Jayasinghe, A. Patel, S. Reid, H. Bayley, Nat. Nanotechnol. 2009, 4, 265.
- 21E. V. B. Wallace, D. Stoddart, A. J. Heron, E. Mikhailova, G. Maglia, T. J. Donohoe, H. Bayley, Chem. Commun. 2010, 46, 8195.
- 22C. Cao, M.-Y. Li, N. Cirauqui, Y.-Q. Wang, M. Dal Peraro, H. Tian, Y.-T. Long, Nat. Commun. 2018, 9, 2823.
- 23Y. Goto, R. Akahori, I. Yanagi, K.-i. Takeda, J. Hum. Genet. 2020, 65, 69.
- 24L. Xue, H. Yamazaki, R. Ren, M. Wanunu, A. P. Ivanov, J. B. Edel, Nat. Rev. Mater. 2020, 5, 931.
- 25J. Li, B. Huang, Y. Wang, A. Li, Y. Wang, Y. Pan, J. Chai, Z. Liu, Y. Zhai, Adv. Mater. 2023, 35, 2210342.
- 26M. A. Alibakhshi, X. Kang, D. Clymer, Z. Zhang, A. Vargas, V. Meunier, M. Wanunu, Adv. Mater. 2023, 35, 2207089.
- 27M. Thakur, M. Macha, A. Chernev, M. Graf, M. Lihter, J. Deen, M. Tripathi, A. Kis, A. Radenovic, Small Methods 2020, 4, 2000072.
- 28K. Chen, A. Choudhary, S. E. Sandler, C. Maffeo, C. Ducati, A. Aksimentiev, U. F. Keyser, Adv. Mater. 2023, 35, 2207434.
- 29S. M. Leitao, V. Navikas, H. Miljkovic, B. Drake, S. Marion, G. P. Blanchet, K. Chen, S. F. Mayer, U. F. Keyser, A. Kuhn, G. E. Fantner, A. Radenovic, Nat. Nanotechnol. 2023, 18, 1078.
- 30T. Gilboa, C. Torfstein, M. Juhasz, A. Grunwald, Y. Ebenstein, E. Weinhold, A. Meller, ACS Nano 2016, 10, 8861.
- 31I. Ohki, N. Shimotake, N. Fujita, M. Nakao, M. Shirakawa, EMBO J. 1999, 18, 6653.
- 32I. Ohki, N. Shimotake, N. Fujita, J.-G. Jee, T. Ikegami, M. Nakao, M. Shirakawa, Cell 2001, 105, 487.
- 33H. F. Jørgensen, K. Adie, P. Chaubert, A. P. Bird, Nucleic Acids Res. 2006, 34, e96.
- 34J. Shim, G. I. Humphreys, B. M. Venkatesan, J. M. Munz, X. Zou, C. Sathe, K. Schulten, F. Kosari, A. M. Nardulli, G. Vasmatzis, R. Bashir, Sci. Rep. 2013, 3, 1389.
- 35J. Shim, Y. Kim, G. I. Humphreys, A. M. Nardulli, F. Kosari, G. Vasmatzis, W. R. Taylor, D. A. Ahlquist, S. Myong, R. Bashir, ACS Nano 2015, 9, 290.
- 36J. Shim, S. Banerjee, H. Qiu, K. K. H. Smithe, D. Estrada, J. Bello, E. Pop, K. Schulten, R. Bashir, Nanoscale 2017, 9, 14836.
- 37A. Sarathy, H. Qiu, J.-P. Leburton, J. Phys. Chem. B. 2017, 121, 3757.
- 38H. Qiu, A. Sarathy, K. Schulten, J.-P. Leburton, npj 2D Mater. Appl. 2017, 1, 3.
- 39S. Li, Y.-C. Lin, X.-Y. Liu, Z. Hu, J. Wu, H. Nakajima, S. Liu, T. Okazaki, W. Chen, T. Minari, Nanoscale 2019, 11, 16122.
- 40A. Reina, H. Son, L. Jiao, B. Fan, M. S. Dresselhaus, Z. Liu, J. Kong, J. Phys. Chem. C 2008, 112, 17741.
- 41A. Storm, J. Chen, X. Ling, H. Zandbergen, C. Dekker, Nat. Mater. 2003, 2, 537.
- 42K. Liu, J. Feng, A. Kis, A. Radenovic, ACS Nano 2014, 8, 2504.
- 43M. Graf, M. Lihter, M. Thakur, S. Georgiou, J. Topolancik, B. R. Ilic, K. Liu, J. Feng, Y. Astier, A. Radenovic, Nat. Protoc. 2019, 14, 1130.
- 44J. Feng, K. Liu, M. Graf, M. Lihter, R. D. Bulushev, D. Dumcenco, D. T. L. Alexander, D. Krasnozhon, T. Vuletic, A. Kis, A. Radenovic, Nano Lett. 2015, 15, 3431.
- 45L. G. Caro, Virology 1965, 25, 226.
- 46P. Renbaum, A. Razin, FEBS Lett. 1992, 313, 243.
- 47S. W. Kowalczyk, D. B. Wells, A. Aksimentiev, C. Dekker, Nano Lett. 2012, 12, 1038.
- 48A. B. Farimani, K. Min, N. R. Aluru, ACS Nano 2014, 8, 7914.
- 49J. Feng, K. Liu, R. D. Bulushev, S. Khlybov, D. Dumcenco, A. Kis, A. Radenovic, Nat. Nanotechnol. 2015, 10, 1070.
- 50F. Wang, C. Zhao, P. Zhao, F. Chen, D. Qiao, J. Feng, Nat. Commun. 2023, 14, 2895.
- 51A. J. Storm, C. Storm, J. Chen, H. Zandbergen, J.-F. Joanny, C. Dekker, Nano Lett. 2005, 5, 1193.
- 52J. Li, M. Gershow, D. Stein, E. Brandin, J. A. Golovchenko, Nat. Mater. 2003, 2, 611.
- 53C. Plesa, C. Dekker, Nanotechnology 2015, 26, 084003.
