Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains

Mei Feng; Nan Wang; Yan Wang; Bi-Jun Xu; Xiao-Gang Wang; Ting-Ting Sun

doi:10.1007/s10118-026-3568-y

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Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains

RESEARCH ARTICLE | Updated：2026-03-26

- Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains
- Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains
- Chinese Journal of Polymer Science 2026年44卷第4期页码：1165-1172
- Affiliations：
  
  a.Department of Physics, Zhejiang University of Science and Technology, Hangzhou 310023, China
  b.Zhejiang Key Laboratory of Biomedical Intelligent Computing Technology, Hangzhou 310008, China
- Author bio：
  
  fengmei@zust.edu.cn (M.F.)
  tingtingsun@zust.edu.cn (T.T.S.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 12302408, 20904047 and 62375245) and the Natural Science Foundation of Zhejiang Province (Nos. LY17A040001 and LY19F03004), the ZUST Postgraduate Course Development Fund (No. 2025yjskj05), and the ZUST Postgraduate Research and Innovation Fund (No. 2025yjskc20).;The authors declare no interest conflict.Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-026-3568-y.The data that support the findings of this study are available from the corresponding author upon reasonable request.
- DOI：10.1007/s10118-026-3568-y
  中图分类号：
- 收稿：2025-12-18，
  
  录用：2026-01-11，
  
  网络首发：2026-03-10，
  
  纸质出版：2026-04-05
- Accepted：
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Feng, M.; Wang, N.; Wang, Y.; Xu, B. J.; Wang, X. G.; Sun, T. T. Length-dependent nanopore transport and surface-induced unfolding of polyglutamine chains. Chinese J. Polym. Sci. 2026, 44, 1165–1172

Mei Feng, Nan Wang, Yan Wang, et al. Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains[J]. Chinese Journal of Polymer Science, 2026, 44(4): 1165-1172.
Feng, M.; Wang, N.; Wang, Y.; Xu, B. J.; Wang, X. G.; Sun, T. T. Length-dependent nanopore transport and surface-induced unfolding of polyglutamine chains. Chinese J. Polym. Sci. 2026, 44, 1165–1172 DOI： 10.1007/s10118-026-3568-y.

Mei Feng, Nan Wang, Yan Wang, et al. Length-dependent Nanopore Transport and Surface-induced Unfolding of Polyglutamine Chains[J]. Chinese Journal of Polymer Science, 2026, 44(4): 1165-1172. DOI： 10.1007/s10118-026-3568-y.

摘要

All-atom molecular dynamics simulations reveal length-dependent nanopore transport and surface-induced unfolding of polyglutamine chains through graphene. Longer chains resist mechanical unfolding with higher force peaks and pulling energy

while slower pulling stabilizes translocation by reducing force fluctuations

providing molecular insight into polyQ conformational regulation.

Abstract

Huntington's disease (HD) is caused by the abnormal expansion of polyglutamine (polyQ) repeats encoded in exon 1 of the huntingtin (HTT) gene

with neurotoxicity typically emerging when the repeat length exceeds 36 glutamine residues. Increasing the polyQ length promotes hypercompact conformations; however

how such compact chains mechanically unfold under nanoconfinement remains insufficiently understood. In this study

all-atom molecular dynamics simulations were performed to investigate the nanopore transport and surface-induced unfolding of polyQ chains of different lengths (Q22

Q36

Q40

and Q46) through graphene nanopores under controlled pulling velocities. By quantitatively analyzing the transport dynamics

as characterized by the pulling force

radius of gyration

center-of-mass distance

interaction energies

number of transported residues

and pulling energy

we demonstrated that polyQ chains of all investigated lengths can successfully translocate through the nanopore and undergo progressive unfolding on the graphene surface over a wide range of pulling velocities. Longer polyQ chains exhibit a higher resistance to unfolding

characterized by enhanced force peaks and increased pulling energy

reflecting stronger intramolecular interactions. Moreover

slower pulling velocities reduce the force fluctuations and lower the overall pulling energy. These results provide molecular-level mechanistic insights into the length-dependent transport and surface-mediated unfolding of polyQ

offering a physical basis for understanding polyQ conformational regulation relevant to Huntington's disease.

关键词

Keywords

references

Walker, F. O. Huntington's disease. Lancet 2007 , 369 , 218−28..

Bates, G. P.; Dorsey, R.; Gusella, J. F.; Hayden, M. R.; Kay, C.; Leavitt, B. R.; Nance, M.; Ross, C. A.; Scahill, R. I.; Wetzel, R.; Wild, E. J.; Tabrizi, S. J. Huntington disease. Nat. Rev. Dis. Primers 2015 , 1 , 15005..

Novak, M. J.; Tabrizi, S. J. Huntington's disease: clinical presentation and treatment. Int. Rev. Neurobiol. 2011 , 98 , 297−323..

MacDonald, M. E.; Ambrose, C. M.; Duyao, M. P.; Myers, R. H.; Lin, C.; Srinidhi, L.; Barnes, G.; Taylor, S. A.; James, M.; Groot, N.; MacFarlane, H.; Jenkins, B.; Anderson, M. A.; Wexler, N. S.; Gusella, J. F.; Bates, G. P.; Baxendale, S.; Hummerich, H.; Kirby, S.; North, M.; Youngman, S.; Mott, R.; Zehetner, G.; Sedlacek, Z.; Poustka, A.; Frischauf, A.-M.; Lehrach, H.; Buckler, A. J.; Church, D.; DoucetteStamm, L.; O’Donovan, M. C.; Riba-Ramirez, L.; Shah, M.; Stanton, V. P.; Strobel, S. A.; Draths, K. M.; Wales, J. L.; Dervan, P.; Housman, D. E.; Altherr, M.; Shiang, R.; Thompson, L.; Fielder, T.; Wasmuth, J. J.; Tagle, D.; Valdes, J.; Elmer, L.; Allard, M.; Castilla, L.; Swaroop, M.; Blanchard, K.; Collins, F. S.; Snell, R.; Holloway, T.; Gillespie, K.; Datson, N.; Shaw, D.; Harper, P. S. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993 , 72 , 971−983..

Lieberman, A. P.; Shakkottai, V. G.; Albin, R. L. Polyglutamine repeats in neurodegenerative diseases. Annu. Rev. Pathol.: Mech. Dis. 2019 , 14 , 1−27..

Wexler, N. S. Huntington's disease: advocacy driving science. Annu. Rev. Med. 2012 , 63 , 1−22..

Hoop, C. L.; Lin, H. K.; Kar, K.; Magyarfalvi, G.; Lamley, J. M.; Boatz, J. C.; Mandal, A.; Lewandowski, J. R.; Wetzel, R.; van der Wel, P. C. A. Huntingtin exon- 1 fibrils feature an interdigitated β-hairpin–based polyglutamine core. P. Natl. Acad. Sci. USA 2016 , 113 , 1546−1551..

Scherzinger, E.; Lurz, R.; Turmaine, M.; Mangiarini, L.; Hollenbach, B.; Hasenbank, R.; Bates, G. P.; Davies, S. W.; Lehrach, H.; Wanker, E. E. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 1997 , 90 , 549−58..

Perutz, M. F.; Johnson, T.; Suzuki, M.; Finch, J. T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. P. Natl. Acad. Sci. USA 1994 , 91 , 5355−5358..

Kang, H.; Vázquez, F. X.; Zhang, L.; Das, P.; Toledo-Sherman, L.; Luan, B.; Levitt, M.; Zhou, R. Emerging β-sheet rich conformations in supercompact huntingtin exon-1 mutant structures. J. Am. Chem. Soc. 2017 , 139 , 8820−8827..

Miettinen, M. S.; Knecht, V.; Monticelli, L.; Ignatova, Z. Assessing polyglutamine conformation in the nucleating event by molecular dynamics simulations. J. Phys. Chem. B. 2012 , 116 , 10259−10265..

Feng, M.; Bell, D. R.; Wang, Z.; Zhang, W. Length-dependent structural transformations of huntingtin polyQ domain upon binding to 2D-nanomaterials. Front. Chem. 2020 , 8 , 299..

Gu, Z.; De Luna, P.; Yang, Z.; Zhou, R. Structural influence of proteins upon adsorption to MoS 2 nanomaterials: comparison of MoS 2 force field parameters. Phys. Chem. Chem. Phys. 2017 , 19 , 3039−3045..

Shen, Y. F.; Luo, M. B. Height-switching of active polymers in binary polymer brushes. Macromolecules 2025 , 58 , 5421−5430..

Luo, M. B.; Shen, Y. F. Langevin dynamics simulations for the critical adsorption of end-grafted active polymers. Soft Matter 2024 , 20 , 5113−5121..

Shen, Y. F.; Luo, M. B. Knotting and adsorption of end-grafted active polymers. Soft Matter 2025 , 21 , 1873−1883..

Lu, C.; Bonini, A.; Viel, J. H.; Maglia, G. Toward single-molecule protein sequencing using nanopores. Nat. Biotechnol. 2025 , 43 , 312−322..

Restrepo-Perez, L.; Soskine, M.; John, S.; Aksimentiev, A.; Maglia, G.; Joo, C.; Dekker, C. Single-molecule protein fingerprinting with nanopores. Biophys. J. 2017 , 112 , 330a..

Hu, H. X.; Shen, Y. F.; Luo, M. B. Translocation of two-dimensional active polymers through nanopores using Langevin dynamics simulations. J. Chem. Phys . 2024 , 160 , 184902..

Wang, C.; Zhou, Y.; Yang, X.; Chen, Y.; Shen, Y.; Luo, M. Conformation and dynamics of a tethered active polymer chain. Phys. Rev. E . 2022 , 106 , 054501..

Miller, J.; Arrasate, M.; Brooks, E.; Libeu, C. P.; Legleiter, J.; Hatters, D.; Curtis, J.; Cheung, K.; Krishnan, P.; Mitra, S.; Widjaja, K.; Shaby, B. A.; Lotz, G. P.; Newhouse, Y.; Mitchell, E. J.; Osmand, A.; Gray, M.; Thulasiramin, V.; Saudou, F.; Segal, M.; Yang, X. W.; Masliah, E.; Thompson, L. M.; Muchowski, P. J.; Weisgraber, K. H.; Finkbeiner, S. Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat. Chem. Biol. 2011 , 7 , 925−934..

Wang, C.; Hu, H. X.; Zhou, Y. L.; Zhao, B.; Luo, M. B. Translocation of a self-propelled polymer through a narrow pore. Chinese J. Polym. Sci. 2022 , 40 , 1670−1678..

Humphrey, W.; Dalke, A.; Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 1996 , 14 , 33−38..

Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983 , 79 , 926−935..

Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 1996 , 118 , 11225..

Best, R. B. Atomistic force fields for proteins. Biomol. Simul. Methods Protoc. 2019 , 2022 , 3−19..

Luan, B.; Huynh, T.; Zhou, R. Complete wetting of graphene by biological lipids. Nanoscale 2016 , 8 , 5750−5754..

Luan, B.; Zhou, R. Wettability and friction of water on a MoS 2 nanosheet. Appl. Phys. Lett . 2016 , 108 , 131601..

Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 2008 , 4 , 435−447..

Páll, S.; Zhmurov, A.; Bauer, P.; Abraham, M.; Lundborg, M.; Gray, A.; Hess, B.; Lindahl, E. Heterogeneous parallelization and acceleration of molecular dynamics simulations in GROMACS. J. Chem. Phys . 2020 , 153 , 134110..

Feng, M.; Chan, K. C.; Zhong, Q.; Zhou, R. In silico design of high-affinity antigenic peptides for HLA-B44. Int. J. Biol. Macromol. 2024 , 267 , 131356..

Feng, M.; Song, Y.; Chen, S. H.; Zhang, Y.; Zhou, R. Molecular mechanism of secreted amyloid-β precursor protein in binding and modulating GABABR1a. Chem. Sci. 2021 , 12 , 6107−6116..

Feng, M.; Bell, D. R.; Kang, H.; Shao, Q.; Zhou, R. Exploration of HIV-1 fusion peptide–antibody VRC34.01 binding reveals fundamental neutralization sites. Phys. Chem. Chem. Phys. 2019 , 21 , 18569−18576..

Darden, T.; Darrin, Y.; Pedersen, L. Particle mesh ewald: an N log (N) method for ewald sums in large systems. J. Chem. Phys. 1993 , 98 , 10089−10089..

Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 2007 , 126 , 014101..

Wexler, N. S.; Lorimer, J.; Porter, J.; Gomez, F.; Moskowitz, C.; Shackell, E.; Marder, K.; Penchaszadeh, G.; Roberts, S. A.; Gayán, J.; Brocklebank, D.; Cherny, S. S.; Cardon, L. R.; Gray, J.; Dlouhy, S. R.; Wiktorski, S.; Hodes, M. E.; Conneally, P. M.; Penney, J. B.; Gusella, J.; Cha, J. H.; Irizarry, M.; Rosas, D.; Hersch, S.; Hollingsworth, Z.; MacDonald, M.; Young, A. B.; Andresen, J. M.; Housman, D. E.; De Young, M. M.; Bonilla, E.; Stillings, T.; Negrette, A.; Snodgrass, S. R.; Martinez-Jaurrieta, M. D.; Ramos-Arroyo, M. A.; Bickham, J.; Ramos, J. S.; Marshall, F.; Shoulson, I.; Rey, G. J.; Feigin, A.; Arnheim, N.; Acevedo-Cruz, A.; Acosta, L.; Alvir, J.; Fischbeck, K.; Thompson, L. M.; Young, A.; Dure, L.; O'Brien, C. J.; Paulsen, J.; Brickman, A.; Krch, D.; Peery , S.; Hogarth, P.; Higgins, D. S., Jr.; Landwehrmeyer, B. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc. Natl. Acad. Sci. USA 2004 , 101 , 3498−3503..

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