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

Rongrong Wu; Xinwen Ou; Liwei Zhang; Xiaolu Song; Zengkai Wang; Mingdong Dong; Lei Liu

doi:10.1021/acs.langmuir.2c02055

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

Rongrong Wu, Xinwen Ou, Liwei Zhang, Xiaolu Song, Zengkai Wang, Mingdong Dong, Lei Liu^*

^*Corresponding author for this work

Interdisciplinary Nanoscience Center - INANO-Fysik, iNANO-huset

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Langmuir
Volume	38
Issue	40
Pages (from-to)	12346-12355
Number of pages	10
ISSN	0743-7463
DOIs	https://doi.org/10.1021/acs.langmuir.2c02055
Publication status	Published - Oct 2022

Keywords

Amyloid
Amyloid beta-Peptides/chemistry
Amyloidogenic Proteins
Diabetes Mellitus, Type 2/complications
Humans
Islet Amyloid Polypeptide/chemistry
Molecular Dynamics Simulation

Access to Document

10.1021/acs.langmuir.2c02055

Cite this

@article{6c0e65bb29d74b2a97effd2c3d882088,

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

abstract = "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.",

keywords = "Amyloid, Amyloid beta-Peptides/chemistry, Amyloidogenic Proteins, Diabetes Mellitus, Type 2/complications, Humans, Islet Amyloid Polypeptide/chemistry, Molecular Dynamics Simulation",

author = "Rongrong Wu and Xinwen Ou and Liwei Zhang and Xiaolu Song and Zengkai Wang and Mingdong Dong and Lei Liu",

year = "2022",

month = oct,

doi = "10.1021/acs.langmuir.2c02055",

language = "English",

volume = "38",

pages = "12346--12355",

journal = "Langmuir",

issn = "0743-7463",

publisher = "American Chemical Society",

number = "40",

}

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 -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this