Solution conditions define morphological homogeneity of α-synuclein fibrils

Sidhu, Arshdeep; Segers-Nolten, Ine; Subramaniam, Vinod

doi:10.1016/j.bbapap.2014.09.007

Cited by 36 publications

(63 citation statements)

References 66 publications

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“…fibrils-65 and -91. Overall, our results agree with those obtained by Sidhu et al 22. on wild-type α-Syn fibrillar assemblies showing that the morphological parameters of height and periodicity in mature α-Syn fibrils are not coupled.…”

Section: Resultssupporting

confidence: 93%

“…The same authors reported one dominant population with average height periodicity of 100 nm in the presence of EDTA22. Our observations suggest that beside divalent ions, pH and the ionic strength affect the overall shape and periodicity of α-syn fibrillar assemblies.…”

Section: Resultssupporting

confidence: 63%

“…Average height periodicities of 50, 100 and 150 nm have been reported for fibrillar assemblies made of wild type and A140C mutant α-syn in 10 mM of Tris buffer at pH 7.4 and in the absence of EDTA22. The same authors reported one dominant population with average height periodicity of 100 nm in the presence of EDTA22.…”

Section: Resultsmentioning

confidence: 80%

“…The abovementioned heterogeneity is incompatible with a straightforward and statistically meaningful characterization of the physical properties of populations of fibrillar α-Syn. As the assembly conditions of α-Syn have been repeatedly shown to influence the nature of the fibrillar particles that form and their homogeneity122233032, we revisited α-Syn assembly into fibrils under tightly controlled experimental conditions. We recently generated two structurally distinct, highly homogeneous, fibrillar α-Syn assemblies1.…”

Section: Resultsmentioning

confidence: 99%

“…In solution, pure α-Syn adopts an intrinsically disordered structure21 and assembles into fibrils that exhibit considerable morphological heterogeneity12223. Such polymorphism may lead to significant differences in fibrils height, width, periodicity, length and mechanical properties.…”

mentioning

confidence: 99%

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

Makky

Bousset

Polesel-Maris

et al. 2016

Sci Rep

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Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson’s disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young’s modulus).

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Section: Resultssupporting

confidence: 93%

Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Makky

Bousset

Polesel-Maris

et al. 2016

Sci Rep

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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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Exploring the potential of amyloids in biomedical applications: A review

Chowdhury,

Sarkar

2023

Biotech & Bioengineering

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Amyloid is defined as a fibrous quaternary structure formed by assembling protein or peptide monomers into intermolecularly hydrogen linked β‐sheets. There is a prevalent issue with protein aggregation and the buildup of amyloid molecules, which results in human neurological illnesses including Alzheimer's and Parkinson's. But it is now evident that many organisms, like bacteria, fungi as well as humans, use the same fibrillar structure to carry out a variety of biological functions, such as structure and protection supporting interface transitions and cell–cell recognition, protein control and storage, epigenetic inheritance, and memory. Recent discoveries of self‐assembling amyloidogenic peptides and proteins, based on the amyloid core structure, give rise to interesting biomaterials with potential uses in numerous industries. These functions dramatically diverge from the initial conception of amyloid fibrils as intrinsically diseased entities. Apart from the natural ability of amyloids to spontaneously arrange themselves and their exceptional material characteristics, this aspect has prompted extensive research into engineering artificial amyloids for generating various nanostructures, molecular substances, and combined materials. Here, we discuss significant developments in the artificial design of useful amyloids as well as how amyloid materials serve as examples of how function emerges from protein self‐assembly at various length scales.

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Solution conditions define morphological homogeneity of α-synuclein fibrils

Cited by 36 publications

References 66 publications

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

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

Interfaces Determine the Fate of Seeded α‐Synuclein Aggregation

Exploring the potential of amyloids in biomedical applications: A review

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