Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics

Hossein Mohammad-Beigi; Seyed Abbas Shojaosadati; Amir Tayaranian Marvian; Jannik Nedergaard Pedersen; Lasse Hyldgaard Klausen; Gunna Christiansen; Jan Skov Pedersen; Mingdong Dong; Dina Morshedi; Daniel E Otzen

doi:10.1039/c5nr05663b

Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics

Hossein Mohammad-Beigi, Seyed Abbas Shojaosadati, Amir Tayaranian Marvian, Jannik Nedergaard Pedersen, Lasse Hyldgaard Klausen, Gunna Christiansen, Jan Skov Pedersen, Mingdong Dong, Dina Morshedi, Daniel E Otzen

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

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Abstract

The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.

Original language	English
Journal	Nanoscale
Volume	7
Pages (from-to)	19627-19640
Number of pages	14
ISSN	2040-3364
DOIs	https://doi.org/10.1039/c5nr05663b
Publication status	Published - 9 Nov 2015

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Mohammad-Beigi, H., Shojaosadati, S. A., Marvian, A. T., Pedersen, J. N., Klausen, L. H., Christiansen, G., Pedersen, J. S., Dong, M., Morshedi, D., & Otzen, D. E. (2015). Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics. Nanoscale, 7, 19627-19640. https://doi.org/10.1039/c5nr05663b

@article{d80df96673e7435faa82c638e5d345d3,

title = "Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics",

abstract = "The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.",

author = "Hossein Mohammad-Beigi and Shojaosadati, {Seyed Abbas} and Marvian, {Amir Tayaranian} and Pedersen, {Jannik Nedergaard} and Klausen, {Lasse Hyldgaard} and Gunna Christiansen and Pedersen, {Jan Skov} and Mingdong Dong and Dina Morshedi and Otzen, {Daniel E}",

year = "2015",

month = nov,

day = "9",

doi = "10.1039/c5nr05663b",

language = "English",

volume = "7",

pages = "19627--19640",

journal = "Nanoscale",

issn = "2040-3364",

publisher = "Royal Society of Chemistry",

}

Mohammad-Beigi, H, Shojaosadati, SA, Marvian, AT, Pedersen, JN, Klausen, LH, Christiansen, G, Pedersen, JS , Dong, M, Morshedi, D & Otzen, DE 2015, 'Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics', Nanoscale, vol. 7, pp. 19627-19640. https://doi.org/10.1039/c5nr05663b

Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics. / Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Marvian, Amir Tayaranian et al.
In: Nanoscale, Vol. 7, 09.11.2015, p. 19627-19640.

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

TY - JOUR

T1 - Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics

AU - Mohammad-Beigi, Hossein

AU - Shojaosadati, Seyed Abbas

AU - Marvian, Amir Tayaranian

AU - Pedersen, Jannik Nedergaard

AU - Klausen, Lasse Hyldgaard

AU - Christiansen, Gunna

AU - Pedersen, Jan Skov

AU - Dong, Mingdong

AU - Morshedi, Dina

AU - Otzen, Daniel E

PY - 2015/11/9

Y1 - 2015/11/9

N2 - The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.

AB - The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.

U2 - 10.1039/c5nr05663b

DO - 10.1039/c5nr05663b

M3 - Journal article

C2 - 26549058

SN - 2040-3364

VL - 7

SP - 19627

EP - 19640

JO - Nanoscale

JF - Nanoscale

ER -

Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics

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