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
- Chinese Journal of Polymer Science Vol. 44, Issue 4, Pages: 1165-1172(2026)
- 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：
- DOI：10.1007/s10118-026-3568-y
  CLC：
- Received：18 December 2025，
  
  Accepted：11 January 2026，
  
  Online First：10 March 2026，
  
  Published：05 April 2026
- Accepted：
Scan QR Code
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.

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references

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