Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

Hossein Mohammad-Beigi; Atiyeh Hosseini; Mohsen Adeli; Mohammad Reza Ejtehadi; Gunna Christiansen; Cagla Sahin; Zhaoxu Tu; Mahdi Tavakol; Arezou Dilmaghani-Marand; Iraj Nabipour; Farshad Farzadfar; Daniel Erik Otzen; Morteza Mahmoudi; Mohammad Javad Hajipour

doi:10.1021/acsnano.8b08983

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

Hossein Mohammad-Beigi, Atiyeh Hosseini, Mohsen Adeli, Mohammad Reza Ejtehadi, Gunna Christiansen, Cagla Sahin, Zhaoxu Tu, Mahdi Tavakol, Arezou Dilmaghani-Marand, Iraj Nabipour, Farshad Farzadfar, Daniel Erik Otzen, Morteza Mahmoudi, Mohammad Javad Hajipour

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

52 Citations (Scopus)

Abstract

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

Original language	English
Journal	ACS Nano
Volume	13
Issue	3
Pages (from-to)	3243-3256
Number of pages	14
ISSN	1936-0851
DOIs	https://doi.org/10.1021/acsnano.8b08983
Publication status	Published - 2019

Keywords

AGGREGATION KINETIC-DATA
BETA-HAIRPIN
CONFORMATION
DOPAMINE
FIBRILLATION
FIBRILLIZATION
NANOPARTICLES
NUCLEATION
PARKINSONS-DISEASE
PATHOGENESIS
Parkinson's disease
alpha-synuclein
electrostatic interaction
fibrillation
graphene
superparamagnetic iron oxide nanoparticles

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10.1021/acsnano.8b08983

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Mohammad-Beigi, H., Hosseini, A., Adeli, M., Ejtehadi, M. R., Christiansen, G., Sahin, C., Tu, Z., Tavakol, M., Dilmaghani-Marand, A., Nabipour, I., Farzadfar, F., Otzen, D. E., Mahmoudi, M., & Hajipour, M. J. (2019). Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein. ACS Nano, 13(3), 3243-3256. https://doi.org/10.1021/acsnano.8b08983

@article{962572d215624fb389bc316f3dd73972,

title = "Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein",

abstract = "Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.",

keywords = "AGGREGATION KINETIC-DATA, BETA-HAIRPIN, CONFORMATION, DOPAMINE, FIBRILLATION, FIBRILLIZATION, NANOPARTICLES, NUCLEATION, PARKINSONS-DISEASE, PATHOGENESIS, Parkinson's disease, alpha-synuclein, electrostatic interaction, fibrillation, graphene, superparamagnetic iron oxide nanoparticles",

author = "Hossein Mohammad-Beigi and Atiyeh Hosseini and Mohsen Adeli and Ejtehadi, {Mohammad Reza} and Gunna Christiansen and Cagla Sahin and Zhaoxu Tu and Mahdi Tavakol and Arezou Dilmaghani-Marand and Iraj Nabipour and Farshad Farzadfar and Otzen, {Daniel Erik} and Morteza Mahmoudi and Hajipour, {Mohammad Javad}",

year = "2019",

doi = "10.1021/acsnano.8b08983",

language = "English",

volume = "13",

pages = "3243--3256",

journal = "ACS Nano",

issn = "1936-0851",

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Mohammad-Beigi, H, Hosseini, A, Adeli, M, Ejtehadi, MR, Christiansen, G, Sahin, C, Tu, Z, Tavakol, M, Dilmaghani-Marand, A, Nabipour, I, Farzadfar, F, Otzen, DE, Mahmoudi, M & Hajipour, MJ 2019, 'Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein', ACS Nano, vol. 13, no. 3, pp. 3243-3256. https://doi.org/10.1021/acsnano.8b08983

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein. / Mohammad-Beigi, Hossein; Hosseini, Atiyeh; Adeli, Mohsen et al.
In: ACS Nano, Vol. 13, No. 3, 2019, p. 3243-3256.

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

TY - JOUR

T1 - Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

AU - Mohammad-Beigi, Hossein

AU - Hosseini, Atiyeh

AU - Adeli, Mohsen

AU - Ejtehadi, Mohammad Reza

AU - Christiansen, Gunna

AU - Sahin, Cagla

AU - Tu, Zhaoxu

AU - Tavakol, Mahdi

AU - Dilmaghani-Marand, Arezou

AU - Nabipour, Iraj

AU - Farzadfar, Farshad

AU - Otzen, Daniel Erik

AU - Mahmoudi, Morteza

AU - Hajipour, Mohammad Javad

PY - 2019

Y1 - 2019

N2 - Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

AB - Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

KW - AGGREGATION KINETIC-DATA

KW - BETA-HAIRPIN

KW - CONFORMATION

KW - DOPAMINE

KW - FIBRILLATION

KW - FIBRILLIZATION

KW - NANOPARTICLES

KW - NUCLEATION

KW - PARKINSONS-DISEASE

KW - PATHOGENESIS

KW - Parkinson's disease

KW - alpha-synuclein

KW - electrostatic interaction

KW - fibrillation

KW - graphene

KW - superparamagnetic iron oxide nanoparticles

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U2 - 10.1021/acsnano.8b08983

DO - 10.1021/acsnano.8b08983

M3 - Journal article

C2 - 30810027

SN - 1936-0851

VL - 13

SP - 3243

EP - 3256

JO - ACS Nano

JF - ACS Nano

IS - 3

ER -

Mechanistic Understanding of the Interactions between Nano-Objects with Different Surface Properties and α-Synuclein

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Keywords

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