Possibilities for ‘smart’ materials exploiting the self-assembly of polypeptides into fibrils

Channon, Kevin J.; MacPhee, Cait E.

doi:10.1039/b713013a

Cited by 56 publications

(42 citation statements)

References 65 publications

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“…In particular, the present results demonstrate a means by which amyloid conformation and biophysical properties can vary with conservation of aggregation propensity and seeding capability. The present results are also of relevance to the emerging biotechnological applications of amyloids (51,52), as it may be possible to achieve a desired physical property of amyloid fibrils (e.g. hydrophilicity) with retention of seeding ability, by manipulating nonessential segments of the amyloid core.…”

Section: Essential and Nonessential Regions Of Prp23-144 Amyloidmentioning

confidence: 75%

Structural Polymorphism in Amyloids

Jones

Surewicz

et al. 2011

Journal of Biological Chemistry

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Background:The Y145Stop prion protein is a useful model for understanding basic principles of amyloid formation. Results: Deletion of the conserved palindrome sequence 113 AGAAAAGA 120 results in an altered amyloid ␤-core without affecting amyloidogenicity or seeding specificity. Conclusion:The core of some amyloids contains "essential" (nucleation-determining) and "nonessential" regions. Significance: This study reveals a novel mechanism for structural polymorphism in amyloids.

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Section: Essential and Nonessential Regions Of Prp23-144 Amyloidmentioning

confidence: 75%

Structural Polymorphism in Amyloids

Jones

Surewicz

et al. 2011

Journal of Biological Chemistry

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“…Understanding the former is essential when designing socalled smart systems that gel under pre-specified conditions [20], whereas the latter is highly relevant to a number of biological applications. For example, recent studies have identified the importance of micro-heterogeneity in the functionality of the extra-cellular matrix [21] and in the vulnerability of healthy tissue to invasion from cancerous cells [22].…”

Section: Introductionmentioning

confidence: 99%

A microrheological study of hydrogel kinetics and micro-heterogeneity

2014

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Abstract. The real-time dynamic heterogeneity of the gelation process of the amino acid derivative Fmoctyrosine (Fmoc-Y) is studied using particle tracking microrheology. To trigger gelation, glucono-δ-lactone (GdL) is added, which gradually lowers the pH over several hours. The onset of self-assembly in the system is signified by a sharp drop in the mean-squared displacement of embedded particles, a phenomenon that is found to correlate with the pH of the system reaching the pK a of Fmoc-Y. The gel point is identified and found to be dependent on the GdL concentration. Analysis of embedded probe particle dynamics allows the heterogeneity of the sample to be quantified, using three metrics: the heterogeneity ratio (HR), the non-Gaussian parameter of the van Hove correlation function (N ) and the bin distribution of the meansquared displacement (MSD) of single particles (f (z)). Results from the three techniques are found to be approximately comparable, with increases in heterogeneity observed in all samples for incubation times t w = 0-3 hours. The final heterogeneity in all samples is found to be remarkably low compared to other systems previously reported in the literature.

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“…Polypeptide fibrils have been suggested as templates for ordering inorganic components in nanoassemblies, [1] or as the basis for biomaterials. [2][3][4] The ordered self-assembly of proteins and polypeptides is also of interest in the context of the protein misfolding disorders, including Alzheimers disease and type 2 diabetes. The vast majority of systems that form amyloid-like fibrils assemble by a nucleation and growth mechanism [5] whereby the formation of a multimeric nucleus of polypeptide molecules drives selfassembly.…”

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confidence: 99%

Characterizing Early Aggregates Formed by an Amyloidogenic Peptide by Mass Spectrometry

Cole¹,

Kalapothakis²,

Bennett³

et al. 2010

Angew Chem Int Ed

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Self-assembly of peptides and proteins into the ordered fibrillar aggregates known as amyloid fibrils has potential for achieving control over molecular-level architecture and macroscopic properties. Polypeptide fibrils have been suggested as templates for ordering inorganic components in nanoassemblies, [1] or as the basis for biomaterials. [2][3][4] The ordered self-assembly of proteins and polypeptides is also of interest in the context of the protein misfolding disorders, including Alzheimers disease and type 2 diabetes. The vast majority of systems that form amyloid-like fibrils assemble by a nucleation and growth mechanism [5] whereby the formation of a multimeric nucleus of polypeptide molecules drives selfassembly. The considerable experimental difficulties associated with observing a small and potentially rare aggregate or aggregates in a soup of molecules have impeded characterization of these triggers to growth.Herein we probe by time-course mass spectrometry (MS) and ion-mobility mass spectrometry (IM-MS) the early aggregation states of an amyloidogenic endecapeptide (sequence YTIAALLSPYS) derived from amino acid residues 105-115 of the human plasma protein transthyretin (TTR 105-115). The mobility K of an ion (and its corresponding reduced mobility K 0 ) is obtained from the arrivaltime distribution (ATD) of a given ion after it has passed through a drift cell filled with a buffer gas under the influence of a weak electric field. K is inversely related to the orientationally averaged collision cross-section W by a modified version of Equation (1):where z is ion charge, e is electron charge, N 0 the buffer gas number density, m the reduced mass of the buffer gas and ion, k B the Boltzmann constant, T the effective temperature, and W is the momentum transfer collision integral.The use of MS methods, and in particular IM-MS, can provide molecular detail on the early stages of aggregation of amyloidogenic peptides and proteins. A large body of work assessing the configurations of species formed during polypeptide aggregation has utilized MS techniques: for example, Bowers and co-workers have examined the self-assembly of Ab, [6] a-synuclein, [7] IAPP, [8] and most recently a prion protein fragment.[9] The unique benefit of this approach is illustrated by a study of early aggregate species formed by the Alzheimers-related peptide Ab1-42 and the non-amyloidogenic variant Ab1-42 F19P (by Bernstein and co-workers [10] ). Resolved species in an ATD following nESI-MS of Ab1-42 were assigned to dimer, tetramer, hexamer, and dodecamer (n = 1, 2, 3, and 6 respectively) whereas the F19P mutant contained only dimer and tetramer. Furthermore, the absence of aggregates intermediate between putative hexamers and dodecamers led the authors to speculate that the hexamer was the building block of protofibril formation, a finding corroborated by cross-linking studies. [11][12][13] Recent work by Ashcroft and co-workers [14] describes the conformation of b2m oligomers up to the tetramer, finding compact dimers and elongate...

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Possibilities for ‘smart’ materials exploiting the self-assembly of polypeptides into fibrils

Cited by 56 publications

References 65 publications

Structural Polymorphism in Amyloids

Structural Polymorphism in Amyloids

A microrheological study of hydrogel kinetics and micro-heterogeneity

Characterizing Early Aggregates Formed by an Amyloidogenic Peptide by Mass Spectrometry

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