Insulin Crystals. V. The Nucleation and Growth of Insulin Crystals.

Schlichtkrull, J.; Ekholm, Reino; Norman, Arne; Noer, B.; Reio, L.

doi:10.3891/acta.chem.scand.11-0439

Cited by 56 publications

(38 citation statements)

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“…However, some have reported signs of homogeneous nucleation in protein crystal growth [10]. Schlichtkrull reported that nucleation can occur within the solution, on the glass solution interface or at the air solution interface for the crystallization of the hormone insulin [11]. The results shown here indicate that a theoretical model which involves only homogenous nucleation will produce the supersaturation decay kinetics observed during lysozyme and canavalin crystal growth.…”

Section: Comparison With Experimentsmentioning

confidence: 64%

Theory of the intermediate stage of crystal growth with applications to protein crystallization

Barlow

2009

Journal of Crystal Growth

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Section: Comparison With Experimentsmentioning

confidence: 64%

Theory of the intermediate stage of crystal growth with applications to protein crystallization

Barlow

2009

Journal of Crystal Growth

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“…In some cases, abundant experimental data have been fitted to engineering or other preconceived models. [16][17][18][19][20][21] In other studies [22][23][24][25] (and references therein), select concepts from the physics of phase transitions were found to well explain some of the features of protein crystal nucleation.…”

Section: Introductionmentioning

confidence: 93%

“…By comparison, insight into first stage of protein crystallization, crystal nucleation, is still very limited. In some cases, abundant experimental data have been fitted to engineering or other preconceived models 16–21 . In other studies 22–25 (and references therein), select concepts from the physics of phase transitions were found to well explain some of the features of protein crystal nucleation.…”

Section: Introductionmentioning

confidence: 99%

Nucleation of Protein Crystals under the Influence of Solution Shear Flow

Penkova¹,

Pan²,

Hodjaoglu³

et al. 2006

Annals of the New York Academy of Sciences

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Several recent theories and simulations have predicted that shear flow could enhance, or, conversely, suppress the nucleation of crystals from solution. Such modulations would offer a pathway for nucleation control and provide a novel explanation for numerous mysteries in nucleation research. For experimental tests of the effects of shear flow on protein crystal nucleation, we found that if a protein solution droplet of approximately 5 microL (2-3 mm diameter at base) is held on a hydrophobic substrate in an enclosed environment and in a quasi-uniform constant electric field of 2 to 6 kV cm(-1), a rotational flow with a maximum rate at the droplet top of approximately 10 microm s(-1) is induced. The shear rate varies from 10(-3) to 10(-1) s(-1). The likely mechanism of the rotational flow involves adsorption of the protein and amphiphylic buffer molecules on the air-water interface and their redistribution in the electric field, leading to nonuniform surface tension of the droplet and surface tension-driven flow. Observations of the number of nucleated crystals in 24- and 72-h experiments with the proteins ferritin, apoferritin, and lysozyme revealed that the crystals are typically nucleated at a certain radius of the droplet, that is, at a preferred shear rate. Variations of the rotational flow velocity resulted in suppression or enhancement of the total number of nucleated crystals of ferritin and apoferritin, while all solution flow rates were found to enhance lysozyme crystal nucleation. These observations show that shear flow may strongly affect nucleation, and that for some systems, an optimal flow velocity, leading to fastest nucleation, exists. Comparison with the predictions of theories and simulations suggest that the formation of ordered nuclei in a "normal" protein solution cannot be affected by such low shear rates. We conclude that the flow acts by helping or suppressing the formation of ordered nuclei within mesoscopic metastable dense liquid clusters. Such clusters were recently shown to exist in protein solutions and to constitute the first step in the nucleation mechanism of many protein and nonproteinsystems.

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“…Extensive R&D work with regard to the process crystallization of polypeptides led to the implementation of the first approved crystalline pharmaceutical polypeptidebiosynthetic human insulin -being successfully marketed on a large-scale basis [1]. This process was based on the early works of Schlichtkrull who was the first to utilize stirred vessels [2] and Randall who used 5-ml shaked centrifuge tubes [3]. The large-scale process was later on developed by E. Lilly & Co. taking place in 500-l stirred batch crystallizers from a purified insulin solution [4].…”

Section: Introductionmentioning

confidence: 99%