2020
DOI: 10.1007/s00249-019-01420-0
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Amyloid formation of bovine insulin is retarded in moderately acidic pH and by addition of short-chain alcohols

Abstract: Protein aggregation and amyloid formation are associated with multiple human diseases, but are also a problem in protein production. Understanding how aggregation can be modulated is therefore of importance in both medical and industrial contexts. We have used bovine insulin as a model protein to explore how amyloid formation is affected by buffer pH and by the addition of short-chain alcohols. We find that bovine insulin forms amyloid fibrils, albeit with different rates and resulting fibril morphologies, acr… Show more

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Cited by 17 publications
(15 citation statements)
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“…Ethanol preferentially binds to the protein, modifies the surrounding hydration layer, and increases the repulsion between molecules. This results in a delay of the aggregation process, which is observed as a prolonged lag-phase in the kinetics [40,41]. A similar effect was observed, when comparing the kinetics for AA spherulites and EtOH spherulites (Fig.…”
Section: Solvent Polarity Controls Spherulite Secondary Structuresupporting
confidence: 73%
“…Ethanol preferentially binds to the protein, modifies the surrounding hydration layer, and increases the repulsion between molecules. This results in a delay of the aggregation process, which is observed as a prolonged lag-phase in the kinetics [40,41]. A similar effect was observed, when comparing the kinetics for AA spherulites and EtOH spherulites (Fig.…”
Section: Solvent Polarity Controls Spherulite Secondary Structuresupporting
confidence: 73%
“…We next examined the morphologies of the insulin aggregates obtained in the presence and in the absence (control) of the chaperonins by AFM ( Figure 7 ). As expected for insulin aggregated at neutral pH [ 21 , 40 ], fibrillary material tends to form short–stumpy fibril clusters ( Figure 7 a), with a different morphology than elongated fibrils typically observed for insulin amyloid species formed at pH 2.2 [ 14 ]. In contrast, a granular species dense network is present in the image from the protein sample incubated with the chaperonins.…”
Section: Resultsmentioning
confidence: 65%
“…Several observations showed how the presence of higher-order oligomeric states in the initial insulin sample is at the basis of a self-inhibition process that determines an unexpected dependence of amyloid aggregation reaction half-times (time at which ThT fluorescence reaches the half-maximum value) on the insulin concentration monomers [ 58 ]. Hence, according to the classical nucleation-polymerisation model, whereas at an acidic pH, the insulin sample, which is essentially populated by monomers/dimers, aggregates with a rate that increases with the concentration, at a neutral pH in which higher-order oligomeric states are predominant, the amyloid formation has an opposite behaviour at varying concentrations [ 21 ]. Probably the higher-order oligomeric states are amyloid off-pathway conformations that do not participate in fibril elongation (thus reducing the low molecular weight species prone to aggregate) or interfere with it.…”
Section: Discussionmentioning
confidence: 99%
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“…By measuring the kinetics of a particular physical parameter of the system, one may obtain the fibrillation kinetics described by a sigmoid curve in most cases. The conventional approach is to determine several parameters from the aggregation kinetic curve such as the duration of the lag phase and the growth rate and to investigate their behavior upon changing parameters of the system, both molecular environment (ionic strength, temperature, protein concentration, the presence of inhibitory molecules) and molecular structure (e.g., by inducing mutations in the protein structure) in order to study the fibrillation process [ 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”
Section: Introductionmentioning
confidence: 99%