Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein

Makky, Ali; Bousset, Luc; Polesel-Maris, Jérôme; Melki, Ronald

doi:10.1038/srep37970

Cited by 57 publications

(74 citation statements)

References 44 publications

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“…The IR and AFM results indicated that an increase in parallel b-sheet contents is the main factor affecting the protein fibrils (Makky, Bousset, Polesel-Maris, & Melki, 2016;Ruggeri et al, 2016). Moreover, our results strongly suggest that oligomerization and/or aggregation is mainly associated with the formation of b-sheet.…”

Section: Discussionmentioning

confidence: 51%

Probing the fibrillation of lysozyme by nanoscale-infrared spectroscopy

Islam

Ali

Popelka

et al. 2020

Journal of Biomolecular Structure and Dynamics

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Amyloid fibrillation is the root cause of several neuro as well as non-neurological disorders. Understanding the molecular basis of amyloid aggregate formation is crucial for deciphering various neurodegenerative diseases. In our study, we have examined the lysozyme fibrillation process using nano-infrared spectroscopy (nanoIR). NanoIR enabled us to investigate both structural and chemical characteristics of lysozyme fibrillar species concurrently. The spectroscopic results indicate that lysozyme transformed into a fibrillar structure having mainly parallel b-sheets, with almost no antiparallel b-sheets. Features such as protein stiffness have a good correlation with obtained secondary structural information showing the state of the protein within the fibrillation state. The structural and chemical details were compared with transmission electron microscopy (TEM) and circular dichroism (CD). We have utilized nanoIR and measured infrared spectra to characterize lysozyme amyloid fibril structures in terms of morphology, molecular structure, secondary structure content, stability, and size of the cross-b core. We have shown that the use of nanoIR can complement other biophysical studies to analyze the aggregation process and is particularly useful for studying proteins involved in aggregation to help in designing molecules against amyloid aggregation. Specifically, the nanoIR spectra afford higher resolution information and a characteristic fingerprint for determining states of aggregation.

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Section: Discussionmentioning

confidence: 51%

Probing the fibrillation of lysozyme by nanoscale-infrared spectroscopy

Islam

Ali

Popelka

et al. 2020

Journal of Biomolecular Structure and Dynamics

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“…Similar values have been reported by other authors for different polymorphs of α‐Syn formed under different solution conditions. [ 25 ] This result indicates that the amyloids formed in absence of AWI are more flexible, have a contour length often higher than their L p , and are therefore more susceptible to thermal breakage, supporting the occasional detection of red‐only fibrils in the dSTORM and correlative LM‐SEM images (panels 3D–F, 4J and 4L). Furthermore, the persistence length of semiflexible polymers L p relates to the Young Modulus E and the second area moment of inertia I via L p = EI / K B T where K B and T are the Boltzmann constant and absolute temperature.…”

Section: Resultsmentioning

confidence: 57%

Interfaces Determine the Fate of Seeded α‐Synuclein Aggregation

Campioni

Bagnani

Pinotsi

et al. 2020

Adv Materials Inter

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Amyloid fibrils formed by the α‐Synuclein (α‐Syn) protein are the pathological hallmark of multiple human disorders, generally termed α‐synucleinopathies. The aggregation process of α‐Syn into amyloids appears to be highly dependent on the presence of: i) hydrophobic–hydrophilic interfaces, and ii) pre‐formed seed fibrils. By combining Thioflavin T binding measurements with different microscopy techniques (direct stochastic optical reconstruction microscopy, atomic force microscopy, correlative super‐resolution light microscopy, and scanning electron microscopy), the effect of the air–water interface (AWI) is tested on seeded α‐Syn aggregation. The correlation of the results provided by each method reveals striking differences in the mechanism of formation, yield, length, thickness, and morphology of fibrils obtained from samples having equal initial amounts of seeds and monomers, but incubated in the presence or absence of an AWI. Overall, the results indicate that the AWI determines how amyloids grow and proliferate, the final balance between monomer and aggregates, and the morphological properties of the aggregates themselves. These observations may set the basis for amplifying and tuning the properties of specific fibril polymorphs of interest, in structural biology and cytotoxicity studies, as well as in those materials science applications featuring amyloids.

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“…α-Syn was incubated in buffer A to obtain the fibrillar polymorph “fibrils” (50 mM Tris–HCl, pH 7.5, 150 mM KCl), in buffer B for “ribbons” (5 mM Tris–HCl, pH 7.5), in buffer C for “fibril-65” (20 mM MES pH6,5, 150 mM NaCl) and in buffer D for “fibril-91” (20 mM KPO4 pH9.1), at 37 °C under continuous shaking in an Eppendorf Thermomixer set at 600 r.p.m for 4–7 days 16 , 40 .…”

Section: Methodsmentioning

confidence: 99%

Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces

Fenyi¹,

Coens²,

Bellande³

et al. 2018

Sci Rep

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α-synuclein fibrillar polymorphs, Tau and Aß 1–42 fibrillar assemblies have been shown to propagate, amplify and trigger the formation of protein deposits reminiscent of those present within the central nervous system of patients developing synucleinopathies, tauopathies and amyloid plaques after injection intracerebrally, intramuscularly, intraperitoneally or within the blood stream of model animals. They are thus hazardous and there is need for decontamination and inactivation procedures for laboratory surfaces and non-disposable material. We assessed the effectiveness of different reagents to clean and disassemble potentially pathogenic assemblies adsorbed on non-disposable materials in laboratories. We show that commercial detergents and SDS are way more suited to detach α-synuclein fibrillar polymorphs, Tau and Aß 1–42 fibrillar assemblies from contaminated surfaces and disassemble the fibrils than methods designed to decrease PrP prion infectivity. Our observations reveal that the choice of the most adapted cleaning procedure for one given protein assembly or fibrillar polymorph should integrate detergent’s cleaning efficiency, material compatibility and capacity to dismantle assemblies. We provide an integrated representation where desorption and neutralization efficacy and surface compatibility are combined to facilitate the choice of the most adapted decontamination procedure. This representation, together with good laboratory practices, contributes to reducing potential health hazards associated to manipulating protein assemblies with prion-like properties.

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Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein

Cited by 57 publications

References 44 publications

Probing the fibrillation of lysozyme by nanoscale-infrared spectroscopy

Probing the fibrillation of lysozyme by nanoscale-infrared spectroscopy

Interfaces Determine the Fate of Seeded α‐Synuclein Aggregation

Assessment of the efficacy of different procedures that remove and disassemble alpha-synuclein, tau and A-beta fibrils from laboratory material and surfaces

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