Effect of Environmental Factors on the Kinetics of Insulin Fibril Formation:  Elucidation of the Molecular Mechanism

Nielsen, Liza; Khurana, Rohit; Coats, Alisa C.; Frøkjær, Sven; Brange, Jens; Vyas, Sandip; Uversky, Vladimir N.; Fink, Anthony L.

doi:10.1021/bi002555c

Cited by 1,085 publications

(1,420 citation statements)

References 51 publications

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“…72 In fact, the influence of agitation can be so profound that, in the case of insulin, it was found to attenuate the effects of other parameters, such as protein concentration and ionic strength, that influence the kinetics of amyloid fibril assembly. 68 …”

Section: Protein Aggregationmentioning

confidence: 99%

The effects of shear flow on protein structure and function

Bekard

Asimakis

Bertolini³

et al. 2011

Biopolymers

140

134

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Toxoplasma gondii usually causes an asymptomatic and then latent infection in human adults; however, a potentially fatal disseminated form can occur in immunocompromised patients. Given that the diagnosis of acute Toxoplasma infection, as opposed to latent disease, relies on finding direct evidence of T. gondii infection in tissue, pathologic examination is critical. There have only been a few reports describing the cytomorphology of Toxoplasma in exfoliative cytology, and no reports of the findings in Thin Prep. In this report, we describe a fatal case of toxoplasmosis in a cardiac transplant patient that was diagnosed by respiratory cytopathology. Although the extracellular organisms were well visualized on the Wright‐Giemsa stained cytospin, they were only faintly seen on the Pap‐stained cytospin trapped within mucin and were not easily appreciated on the ThinPrep slides nor the H&E stained cell block sections. An immunohistochemical stain for Toxoplasma performed on the cell block was strongly positive, and an autopsy performed on the patient confirmed disseminated infection. Our case illustrates that the diagnosis of Toxoplasma in exfoliative cytology specimens can be challenging since organisms are not well visualized on ThinPrep or Pap‐stained material; therefore, Wright‐Giemsa stained material can be particularly helpful. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.

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Section: Protein Aggregationmentioning

confidence: 99%

The effects of shear flow on protein structure and function

Bekard

Asimakis

Bertolini³

et al. 2011

Biopolymers

140

134

View full text Add to dashboard Cite

show abstract

“…Enhanced formation of different protein fibril systems by addition of preformed fibrils (seeding) has previously been established. [16][17][18] Another possibility is inducing a mechanical disturbance in the system. In insulin solutions, continuous agitation was shown to enhance the fibril formation.…”

Section: Introductionmentioning

confidence: 99%

“…In insulin solutions, continuous agitation was shown to enhance the fibril formation. 17 Unfortunately, these experiments were not performed in a well-defined flow field. Stathopulos et al 18 found that sonication of a diverse group of proteins resulted in the formation of fibrils.…”

Section: Introductionmentioning

confidence: 99%

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Shear Pulses Nucleate Fibril Aggregation

et al. 2006

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We have studied the effect of shear flow on the formation of amyloid fibrils of the whey protein blactoglobulin. b-Lactoglobulin aggregates into long, thin, and semiflexible fibrils upon heating at low pH and low ionic strength. Solutions with a protein concentration of 0.5% (w/w) were used, and the formation of fibrils was quantified with flow-induced birefringence, a proportional measure of the length concentration of the fibrils. From the decay of the birefringence after cessation of the flow, a length distribution could be fitted. Pulsed and continuous shear treatment of the samples resulted in a comparable enhancement of the fibrillar growth as compared to the fibrillar growth under quiescent conditions. This indicates that the onset of shear flow is the key parameter for the enhancement of fibrillar growth and not the continuous shear flow itself. This behavior is comparable to a nucleation-like process, during which preaggregates of the fibrils are induced during the onset of the flow and orthokinetic coagulation is absent. However, a difference was present in the length distribution between the pulsed and continuously sheared samples, which can be explained by the homogenizing effect of shear flow.

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“…The nucleation step is known to have a high activation energy barrier, which results in a distinct lag phase during assembly kinetics [10]. Various environmental factors such as pH, ionic strength and the presence of seeds affect the lag phase of amyloid assembly [11,12]. In addition to studies in bulk solution, amyloid formation on surfaces has been actively investigated since it may more closely mimic physiological environments such as cell membrane [13].…”

Section: Amyloid Nanofibermentioning

confidence: 99%

Direct Observation of Amyloid Nucleation under Nanomechanical Stretching

et al. 2013

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Self-assembly of amyloid nanofiber is associated with functional and pathological processes such as in neurodegenerative diseases. Despite intensive studies, stochastic nature of the process has made it difficult to elucidate molecular mechanisms for the key amyloid nucleation. Here, we investigated the amyloid nucleation of silk-elastinlike peptide (SELP) using time-lapse lateral force microscopy (LFM). By repeated scanning a single line on a SELP-coated mica surface, we observed sudden stepwise height increases, corresponds to nucleation of an amyloid fiber. The lateral force profiles followed either a worm-like chain model or an exponential function, suggesting that the atomic force microscopy (AFM) tip stretches a single or multiple SELP molecules along the scanning direction, serves as the template for further selfassembly perpendicular to the scan direction. Such mechanically induced nucleation of amyloid fibrils allows positional and directional control of amyloid assembly in vitro, which we demonstrate by generating single nanofibers at predetermined nucleation sites.

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Effect of Environmental Factors on the Kinetics of Insulin Fibril Formation: Elucidation of the Molecular Mechanism

Cited by 1,085 publications

References 51 publications

The effects of shear flow on protein structure and function

The effects of shear flow on protein structure and function

Shear Pulses Nucleate Fibril Aggregation

Direct Observation of Amyloid Nucleation under Nanomechanical Stretching

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