The role of surfaces on amyloid formation

Grigolato, Fulvio; Arosio, Paolo

doi:10.1016/j.bpc.2020.106533

Cited by 64 publications

(62 citation statements)

References 203 publications

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“…Models of the mechanistic influence of surfaces on peptide nucleation and aggregation have previously been reported and summarized. 5,9,30,48…”

Section: Resultsmentioning

confidence: 99%

“…5,[17][18][19][20] These paradoxical effects result from the diversity of NPs which are characterized by varying physicochemical properties, determined by their material, 9 surface chemistry, [21][22][23] morphology and size. [24][25][26][27][28][29][30] NP size effects on amyloid peptide aggregation have been the subject of intense research. 18, [25][26][27]29,31,32 Experimental studies identified an impact on the immediate peptide layer formed around NPs, the corona, 31 and particularly the peptide's secondary structure 18,26 and β-sheet content.…”

Section: Introductionmentioning

confidence: 99%

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Size Matters: A Mechanistic Model of Nanoparticle Curvature Effects on Amyloid Fibril Formation

John

Adler

Elsner

et al. 2021

Preprint

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The aggregation of peptides into amyloid fibrils is linked to ageing-related diseases, such as Alzheimer's disease and type 2 diabetes. Interfaces, particularly those with large nanostructured surface areas, can affect the kinetics of peptide aggregation, ranging from a complete inhibition to strong acceleration. While a number of physiochemical parameters determine interface effects, we here focus on the role of nanoparticle curvature for the aggregation of the amyloidogenic peptides Aβ40, NNFGAIL, GNNQQNY and VQIYVK. Nanoparticles (NPs) provided a surface for peptide monomers to adsorb, enabling the nucleation into oligomers and fibril formation. High surface curvature, however, destabilized prefibrillar structures, providing an explanation for inhibitory effects on fibril growth. Thioflavin T (ThT) fluorescence assays as well as dynamic light scattering (DLS), atomic force microscopy (AFM) and electron microscopy experiments revealed NP size-dependent effects on amyloid fibril formation, with differences between the peptides. While 5 nm gold NPs (AuNP-5) retarded or inhibited the aggregation of most peptides, larger 20 nm gold NPs (AuNP-20) tended to accelerate peptide aggregation. Molecular dynamics (MD) studies demonstrated that NPs' ability to catalyze or inhibit oligomer formation was influenced by the oligomer stability at curved interfaces which was lower at more highly curved surfaces. Differences in the NP effects for the peptides resulted from the peptide properties (size, aggregation propensity) and concomitant surface binding affinities. The results can be applied to the design of future nanostructured materials for defined applications.

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“…Models of the mechanistic influence of surfaces on peptide nucleation and aggregation have previously been reported and summarized. 5,9,30,48…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Size Matters: A Mechanistic Model of Nanoparticle Curvature Effects on Amyloid Fibril Formation

John

Adler

Elsner

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…However, this often requires the destabilization of the native protein structure, for instance, by non-physiological pH, ionic strength, temperature, or monomer concentration. While it was already shown thirty years ago that the presence of interfaces can also stimulate protein and peptide aggregation [ 31 ], surface- and interface-related effects have only recently become a focus of attention [ 32 , 33 , 34 ]. This recent development was mostly motivated by the potential of nanoparticle-based strategies to mitigate amyloid-associated diseases [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], as well as by promising applications of amyloid fibrils in materials’ synthesis [ 44 , 45 , 46 , 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

“…This recent development was mostly motivated by the potential of nanoparticle-based strategies to mitigate amyloid-associated diseases [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], as well as by promising applications of amyloid fibrils in materials’ synthesis [ 44 , 45 , 46 , 47 , 48 ]. Nevertheless, the manifold effects of the physicochemical surface properties on amyloid aggregation and the involved molecular mechanisms are far from understood [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces

Hanke

Yang

et al. 2021

IJMS

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The effects that solid–liquid interfaces exert on the aggregation of proteins and peptides are of high relevance for various fields of basic and applied research, ranging from molecular biology and biomedicine to nanotechnology. While the influence of surface chemistry has received a lot of attention in this context, the role of surface topography has mostly been neglected so far. In this work, therefore, we investigate the aggregation of the type 2 diabetes-associated peptide hormone hIAPP in contact with flat and nanopatterned silicon oxide surfaces. The nanopatterned surfaces are produced by ion beam irradiation, resulting in well-defined anisotropic ripple patterns with heights and periodicities of about 1.5 and 30 nm, respectively. Using time-lapse atomic force microscopy, the morphology of the hIAPP aggregates is characterized quantitatively. Aggregation results in both amorphous aggregates and amyloid fibrils, with the presence of the nanopatterns leading to retarded fibrillization and stronger amorphous aggregation. This is attributed to structural differences in the amorphous aggregates formed at the nanopatterned surface, which result in a lower propensity for nucleating amyloid fibrillization. Our results demonstrate that nanoscale surface topography may modulate peptide and protein aggregation pathways in complex and intricate ways.

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“…In recent times, several strategies have been fortified to study various aspects of amyloid fibrillation using NMR. 3 , 29 , 30 Solution NMR is extensively used for studying the structure, function, and dynamics of polypeptides and thus proves to be an excellent technique in studying aggregation of amyloidogenic polypeptides. 31 − 34 In recent times, advanced NMR technologies such as high magnetic field experimentation and dissolution dynamic nuclear polarization have paved way to attain a higher-resolution insight into the fibrillation mechanism using solution NMR spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

Biophysical Investigation of the Interplay between the Conformational Species of Domain-Swapped GB1 Amyloid Mutant through Real–Time Monitoring of Amyloid Fibrillation

et al. 2021

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Mutant polypeptide GB1HS#124 F26A , which is known to aggregate into amyloid-like fibrils, has been utilized as a model in this study for gaining insights into the mechanism of domain-swapped aggregation through real-time monitoring. Size exclusion with UV monitoring at 280 nm and dynamic light scattering (DLS) profiles through different time points of fibrillation reveal that the dimer transitions into monomeric intermediates during the aggregation, which could further facilitate domain swapping to form amyloid fibrils. The 1D 1 H and 2D 1 H– 13 C HSQC nuclear magnetic resonance (NMR) spectra profiling through different time points of fibrillation reveal that there may be some other species present along with the dimer during aggregation which contribute to different trends for the intensity of protons in the spectral peaks. Diffusion NMR reveals changes in the mobility of the dimeric species during the process of aggregation, indicating that the dimer gives rise to other lower molecular weight species midway during aggregation, which further add up to form the oligomers and amyloid fibrils successively. The present work is a preliminary study which explores the possibility of utilizing biophysical methods to gain atomistic level insights into the different stages of aggregation.

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The role of surfaces on amyloid formation

Cited by 64 publications

References 203 publications

Size Matters: A Mechanistic Model of Nanoparticle Curvature Effects on Amyloid Fibril Formation

Size Matters: A Mechanistic Model of Nanoparticle Curvature Effects on Amyloid Fibril Formation

Nanoscale Surface Topography Modulates hIAPP Aggregation Pathways at Solid–Liquid Interfaces

Biophysical Investigation of the Interplay between the Conformational Species of Domain-Swapped GB1 Amyloid Mutant through Real–Time Monitoring of Amyloid Fibrillation

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