Nanopore‐Based, Rapid Characterization of Individual Amyloid Particles in Solution: Concepts, Challenges, and Prospects

Mayer, Michael; List, Jonathan

doi:10.1002/smll.201802412

Cited by 60 publications

(76 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We hope that this overview will be helpful for solving or minimizing some of the problems that hamper the usefulness of nanopore-based analytics of complex, real world samples. 275 We predict that the nanopore field will continue to expand the strategies for increasing the functionality of nanopores 300 and nanocapillaries [301][302][303] and that coatings will play an essential role in this development. We expect to witness an increase, both in the number of ways how coatings will be applied, and in the fine-tuning of their molecular composition.…”

Section: Discussionmentioning

confidence: 99%

“…155 Specifically, the authors suggested that Tween 20 application to silicon nitride nanopores rendered the surface more hydrophilic (as confirmed by contact angle experiments), minimizing adhesion of the protein alpha-synuclein that is implicated in Parkinson's disease. 275 This modification allowed for the identification of four types of alpha-synuclein oligomers 155 as well as the differentiation between ssDNA and dsDNA. 156 Xie et al tested CTAB for generating a coating that inverted the negative surface charge of track-etched nanopores in PET foils to a surface with a positive charge.…”

Section: Surfactant-based Nanopore Coatingsmentioning

confidence: 99%

“…In one example, our group took advantage of lipid coatings to investigate the aggregation of amyloidβ oligomers, which are associated with neurodegenerative diseases such as Alzheimer's disease. 259,275 Without the fluid lipid coating these experiments typically ended within seconds because amyloid-β samples clogged uncoated nanopores in silicon nitride membranes 298 while lipid coatings enabled recordings for more than 40 min. More recently, we took advantage of the reduced translocation speed of lipidanchored proteins to characterize them on the single molecule level by determining their shape, rotational diffusion coefficient, dipole moment, and charge.…”

Section: Fluid Lipid Coatingsmentioning

confidence: 99%

See 2 more Smart Citations

Surface coatings for solid-state nanopores

2019

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Surfactant-based Nanopore Coatingsmentioning

confidence: 99%

Section: Fluid Lipid Coatingsmentioning

confidence: 99%

See 1 more Smart Citation

Surface coatings for solid-state nanopores

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…By analyzing the amplitudes, durations and shapes of the events, the size, conformational changes and interactions with other molecules can be determined at a SM level. Recently, single-nanopore technologies have shown great potential for the characterization of individual amyloid proteins (Houghtaling et al, 2018), which will be further discussed. Zhao et al (2009) studied the translocation of Aβ10-20 and various short peptides through an engineered α-HL nanopore.…”

Section: Biological Nanoporesmentioning

confidence: 99%

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Cao

Loch

et al. 2020

Quart. Rev. Biophys.

View full text Add to dashboard Cite

In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and α-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed.

show abstract

“…[ 25 ] This makes them a candidate to develop new analytical tools for amyloid sensing. [ 26 ] However, their diameter and their short lifetime don't allow protofibril detection nor long time analysis. We recently reported that conical track‐etched nanopore is likely the most suitable candidate to investigate the protein aggregation from small aggregates to protofibrils scale.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Food Amyloid Protein Digestion by Conical Nanopore

et al. 2020

View full text Add to dashboard Cite

from β-lactoglobulin show several interesting features, such as the high aspect ratio (length vs diameter) making them a structuring agent in foods, stabilizers of foam and in emulsions as well as building blocks of microcapsules. [8] The applications of β-lactoglobulin fibrils in food products require a deep understanding of fibril digestion processes occurring during passage through the stomach and the intestine. [9] Indeed, certain amyloids such as tau, α-synuclein or β-peptides are involved in neurodegenerative diseases. [10] The protein fibril digestion can cleave the fibrils to oligomers with a potential increased pathogenic [11,12] or contribute to the formation of new fibrils as seeds. [13] To date, the investigation of the nondisease-related amyloid-like fibrils degradation combining kinetic and identification of species are difficult due to the difficulty to obtain both information using the same technique. Nanopore technology is one of the most promising approaches to protein sensing. [14,15] It allows single molecule detection providing information about the size, shape as well as charge. [16,17,18] Nanopores are also a platform to characterize the protein conformational change including folding/ unfolding. [19] Biological nanopores take advantage of their precise structure, allowing the characterization of polypeptide length and the identification of amino-acids, [20] opening a new avenue for protein sequencing. [21,22] On the other hand, they were used to detect small oligomers of peptides [23] and antibody prion interactions. [24] Solid-state nanopores and nanopipettes allow the characterization of the protein and peptide oligomerization giving also information on their morphology. [25] This makes them a candidate to develop new analytical tools for amyloid sensing. [26] However, their diameter and their short lifetime don't allow protofibril detection nor long time analysis. We recently reported that conical track-etched nanopore is likely the most suitable candidate to investigate the protein aggregation from small aggregates to protofibrils scale. [27] In this report, β-lactoglobulin aggregation was studied, discriminating between oligomer and protofibril populations. In addition, the long nanopore lifetime and the possibility to perform long time experiments, is suitable to analyze the digestion of β-lactoglobulin aggregates. The most relevant physiological proteases in digestion process are pepsin (stomach) and trypsin (small intestine). β-lactoglobulin aggregates are used as structuring agents in food processing. Their enzymatic degradation follows different pathways depending on the enzyme and the pH. The transient species produced during the degradation process are difficult to characterize under continuous measurement. Here, conical track-etched nanopores are used to investigate the β-lactoglobulin degradation by pepsin (pH 2) and trypsin (pH 9). Before enzyme addition, two distinct populations, oligomers and protofibrils, are identified. Just after enzyme addition, the aggregate size decr...

show abstract

Nanopore‐Based, Rapid Characterization of Individual Amyloid Particles in Solution: Concepts, Challenges, and Prospects

Cited by 60 publications

References 136 publications

Surface coatings for solid-state nanopores

Surface coatings for solid-state nanopores

Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives

Characterization of Food Amyloid Protein Digestion by Conical Nanopore

Contact Info

Product

Resources

About