Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway

TY - JOUR

T1 - Electric Field Effect on Inhibiting the Co-fibrillation of Amyloid Peptides by Modulating the Aggregation Pathway

AU - Wu, Rongrong

AU - Ou, Xinwen

AU - Zhang, Liwei

AU - Song, Xiaolu

AU - Wang, Zengkai

AU - Dong, Mingdong

AU - Liu, Lei

PY - 2022/10

Y1 - 2022/10

N2 - With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of β-amyloid peptide (Aβ) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the β-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from β-sheet to random coil, the strong interaction between Aβ and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

AB - With the revelation of the close link between Alzheimer's disease (AD) and type II diabetes (T2D) and the possible assembly of multiple amyloid peptides therein, it is critical to understand and regulate the co-fibrillation pathway between related amyloid peptides. Here, we show experimentally and theoretically that electric field (EF) inhibited hybrid amyloid fibrillation of β-amyloid peptide (Aβ) and human islet amyloid peptide (hIAPP) by modulating the hetero-aggregation pathway. Experimental results confirm that the β-sheet secondary structure of amyloid peptides would be disrupted under small static EF and accompanied by transforming fibril aggregates into amorphous particles in vitro. Molecular dynamics simulations further demonstrate that even with the transformation of the secondary structure from β-sheet to random coil, the strong interaction between Aβ and hIAPP peptides would remain largely unaffected under the small static EF, leading to the formation of amorphous nanoparticles observed in the experiments. This inhibitory effect of EF on the co-fibrillation of multiple amyloid peptides might contribute to reducing the mutual deterioration of different degenerative diseases and show great potential for the noninvasive treatment of amyloid-related diseases.

KW - Amyloid

KW - Amyloid beta-Peptides/chemistry

KW - Amyloidogenic Proteins

KW - Diabetes Mellitus, Type 2/complications

KW - Humans

KW - Islet Amyloid Polypeptide/chemistry

KW - Molecular Dynamics Simulation

UR - http://www.scopus.com/inward/record.url?scp=85139431576&partnerID=8YFLogxK

U2 - 10.1021/acs.langmuir.2c02055

DO - 10.1021/acs.langmuir.2c02055

M3 - Journal article

C2 - 36173231

AN - SCOPUS:85139431576

SN - 0743-7463

VL - 38

SP - 12346

EP - 12355

JO - Langmuir

JF - Langmuir

IS - 40

ER -