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Peer-reviewedCC BYJACS Au

Membranes Decouple α‑Synuclein Surface Assembly and Kinetic Restriction from Persistent Amyloid-like Intermolecular Organization.

  • Jinyu Chen1
  • Xiakun Chu1,2,3
  1. 1Advanced Materials Thrust, Function Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511453, China.
  2. 2Guangzhou Municipal Key Laboratory of Materials Informatics, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong 511453, China.
  3. 3Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.
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Abstract

Membrane association places α-synuclein (αSyn) at the boundary between physiological surface organization and pathological amyloid assembly, supporting vesicle clustering, surface condensation, and amyloid nucleation. How interfacial recruitment, condensate cohesion, and persistent amyloid-like organization are coupled or decoupled remains unclear. Because membrane binding also induces helical ordering in the N-terminal membrane-binding region and the aggregation-prone non-amyloid-β component (NAC) region, we used multichain coarse-grained simulations to separate conformational ordering from recruitment by an anionic POPC/POPG bilayer. Helical/ordered segments promoted locally dense, directionally packed assemblies but weakened global condensate cohesion. Membrane association produced flattened surface assemblies and increased the protein population outside the largest condensate. Despite becoming dynamically restricted, these membrane-associated condensates did not show systematically prolonged NAC contact lifetimes. Thus, membrane-driven surface assembly and kinetic restriction can be decoupled from persistent amyloid-like intermolecular organization, explaining how lipid interfaces promote αSyn clustering without necessarily driving amyloid-competent organization.

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Cite

BibTeXRIS
BibTeX
@article{chen2026membranes,
  title = {{Membranes Decouple α‑Synuclein Surface Assembly and Kinetic Restriction from Persistent Amyloid-like Intermolecular Organization.}},
  author = {Jinyu Chen and Xiakun Chu},
  journal = {JACS Au},
  year = {2026},
  month = sep,
  doi = {10.1021/jacsau.6c01222},
  url = {https://europepmc.org/article/MED/42953625},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Membranes Decouple α‑Synuclein Surface Assembly and Kinetic Restriction from Persistent Amyloid-like Intermolecular Organization.
AU  - Jinyu Chen
AU  - Xiakun Chu
PY  - 2026
DA  - 2026/09/01
JO  - JACS Au
DO  - 10.1021/jacsau.6c01222
UR  - https://europepmc.org/article/MED/42953625
AB  - Membrane association places α-synuclein (αSyn) at the boundary between physiological surface organization and pathological amyloid assembly, supporting vesicle clustering, surface condensation, and amyloid nucleation. How interfacial recruitment, condensate cohesion, and persistent amyloid-like organization are coupled or decoupled remains unclear. Because membrane binding also induces helical ordering in the N-terminal membrane-binding region and the aggregation-prone non-amyloid-β component (NAC) region, we used multichain coarse-grained simulations to separate conformational ordering from recruitment by an anionic POPC/POPG bilayer. Helical/ordered segments promoted locally dense, directionally packed assemblies but weakened global condensate cohesion. Membrane association produced flattened surface assemblies and increased the protein population outside the largest condensate. Despite becoming dynamically restricted, these membrane-associated condensates did not show systematically prolonged NAC contact lifetimes. Thus, membrane-driven surface assembly and kinetic restriction can be decoupled from persistent amyloid-like intermolecular organization, explaining how lipid interfaces promote αSyn clustering without necessarily driving amyloid-competent organization.
SN  - 2691-3704
ER  -