Voltage-driven Structural Modulation of Single Enzyme Molecules with Nanopipettes

doi:10.1007/s40242-026-6169-y

Chemical Research in Chinese Universities ›› 2026, Vol. 42 ›› Issue (5): 1504-1508.doi: 10.1007/s40242-026-6169-y

• Research Articles • Previous Articles Next Articles

Voltage-driven Structural Modulation of Single Enzyme Molecules with Nanopipettes

ZHANG Cuiju¹, CHEN Wenlong^1,2, DENG Simeng¹, DENG Fan¹, MA Hui^1,2

1. School of Chemistry and Chemical Engineering, Zhejiang Sci-Tech University, Hangzhou 310038, P. R. China;
2. School of Materials Science & Engineering, Zhejiang Sci-Tech University, Hangzhou 310038, P. R. China

Received:2026-07-09 Accepted:2026-08-29 Online:2026-10-01 Published:2026-09-24
Supported by:
This work was supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars, China (No. LR25B050001), and the Science Foundation of Zhejiang Sci-Tech University, China (No. 24262198-Y).

Abstract

Abstract: Electric-field modulation of protein structure has attracted increasing interest, yet quantitative characterization under nanoconfinement remains challenging. Here, we investigate the voltage-dependent translocation of formate dehydrogenase (FDH) through a nanopipette. The ionic current blockade increases linearly between 300 and 500 mV before deviating from the low-voltage trend at higher voltages, accompanied by corresponding changes in dwell time and event frequency. Quantitative analysis of ionic current blockades reveals a progressive reduction in the effective excluded volume of FDH, decreasing by approximately 13% at 600 mV and 23% at 700 mV relative to the low-voltage range. These findings suggest the electric field can serve as a modulator of FDH conformation during translocation, highlighting its dual role in both driving transport and modulating protein structure at the single-molecule level.

Key words: Nanopipette, Single-molecule sensing, Structural modulation

ZHANG Cuiju, CHEN Wenlong, DENG Simeng, DENG Fan, MA Hui. Voltage-driven Structural Modulation of Single Enzyme Molecules with Nanopipettes[J]. Chemical Research in Chinese Universities, 2026, 42(5): 1504-1508.

References

[1] Corbella M., Pinto G. P., Kamerlin S. C. L., Nat. Rev. Chem., 2023, 7, 536
[2] Torgeson K. R., Clarkson M. W., Granata D., Lindorff-Larsen K., Page R., Peti W., Sci. Adv., 2022, 8, eabo5546.
[3] Hegazy R., Richard J. P., Chem. Rev., 2025, 125, 11524.
[4] Mondal D., Snodgrass H. M., Gomez C. A., Lewis J. C., Chem. Rev., 2023, 123, 10381.
[5] Secundo F., Chem. Soc. Rev., 2013, 42, 6250.
[6] Dong L., Li L., Chen H., Cao Y., Lei H., Adv. Sci., 2025, 12, e2403949.
[7] Olivares A. O., Baker T. A., Sauer R. T., Annu. Rev. Physiol., 2018, 80, 413.
[8] Edwards D. T., LeBlanc M. A., Perkins T. T., Proc. Natl. Acad. Sci. U. S. A., 2021, 118, e2015728118.
[9] Gokulu I. S., Banta S., ACS Synth. Biol., 2024, 13, 2600.
[10] Wang Y. Y., Ma H., Long Y. T., Ying Y. L., Chem. Res. Chinese Universities, 2024, 40, 272.
[11] Ying Y. L., Yang C. N., Liu W., Wu X. Y., Long Y. T., Nat. Chem., 2025, 17, 1450.
[12] Ansah I. B., Joardar S., Freedman K. J., J. Am. Chem. Soc., 2026, 148, 15797.
[13] Ahmed S. A., Liu Y., Xiong T., Zhao Y., Xie B., Pan C., Ma W., Yu P., Anal. Chem., 2024, 96, 8056.
[14] Brucale M., Schuler B., Samorì B., Chem. Rev., 2014, 114, 3281.
[15] Yusko E. C., Bruhn B. R., Eggenberger O. M., Houghtaling J., Rollings R. C., Walsh N. C., Nandivada S., Pindrus M., Hall A. R., Sept D., Li J., Kalonia D. S., Mayer M., Nat. Nanotechnol., 2017, 12, 360.
[16] Sze J. Y. Y., Ivanov A. P., Cass A. E. G., Edel J. B., Nat. Commun., 2017, 8, 1552.
[17] Ma H., Wang Y., Li Y. X., Xie B. K., Hu Z. L., Yu R. J., Long Y. T., Ying Y. L., J. Am. Chem. Soc., 2024, 146, 28014.
[18] Pan R., Wang D., Liu K., Chen H. Y., Jiang D., J. Am. Chem. Soc., 2022, 144, 17558.
[19] Bandara Y. M. N. D. Y., Freedman K. J., J. Am. Chem. Soc., 2024, 146, 3171.
[20] Wang X., Wilkinson M. D., Lin X., Ren R., Willison K. R., Ivanov A. P., Baum J., Edel J. B., Chem. Sci., 2019, 11, 970.
[21] Fologea D., Ledden B., McNabb D. S., Li J., Appl. Phys. Lett., 2007, 91, 053901.
[22] Guo Q., Gakhar L., Wickersham K., Francis K., Vardi-Kilshtain A., Major D. T., Cheatum C. M., Kohen A., Biochemistry, 2016, 55, 2760.
[23] He L., Luo Y. C., Zhang Y., Tan T. F., Liu J. Q., Chem. Res. Chinese Universities, 2025, 41, 95.
[24] Yoshimoto M., Yamashita T., Yamashiro T., Biotechnol. Prog., 2010, 26, 1047.
[25] Ying Y. L., Hu Z. L., Zhang S., Qing Y., Fragasso A., Maglia G., Meller A., Bayley H., Dekker C., Long Y. T., Nat. Nanotechnol., 2022, 17, 1136.
[26] Schmid S., Stömmer P., Dietz H., Dekker C., Nat. Nanotechnol., 2021, 16, 1244.
[27] Talaga D. S., Li J., J. Am. Chem. Soc., 2009, 131, 9287.
[28] Sadhu S., Soni G. V., Nanoscale, 2025, 17, 25740.
[29] Bakouei M., Abdorahimzadeh S., Taghipoor M., Phys. Chem. Chem. Phys., 2020, 22, 25306.
[30] Neuman K. C., Nagy A., Nat. Methods., 2008, 5, 491.

Voltage-driven Structural Modulation of Single Enzyme Molecules with Nanopipettes

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 1

Recommended Articles

Metrics

Comments