Factors affecting the formation of insulin amyloid spherulites

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Factors affecting the formation of insulin amyloid spherulites. / Smith, M I.; Foderà, Vito; Sharp, James S; Roberts, Clive J; Donald, Athene M.

In: Colloids and Surfaces B: Biointerfaces, Vol. 89, 01.01.2012, p. 216-22.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Smith, MI, Foderà, V, Sharp, JS, Roberts, CJ & Donald, AM 2012, 'Factors affecting the formation of insulin amyloid spherulites', Colloids and Surfaces B: Biointerfaces, vol. 89, pp. 216-22. https://doi.org/10.1016/j.colsurfb.2011.09.018

APA

Smith, M. I., Foderà, V., Sharp, J. S., Roberts, C. J., & Donald, A. M. (2012). Factors affecting the formation of insulin amyloid spherulites. Colloids and Surfaces B: Biointerfaces, 89, 216-22. https://doi.org/10.1016/j.colsurfb.2011.09.018

Vancouver

Smith MI, Foderà V, Sharp JS, Roberts CJ, Donald AM. Factors affecting the formation of insulin amyloid spherulites. Colloids and Surfaces B: Biointerfaces. 2012 Jan 1;89:216-22. https://doi.org/10.1016/j.colsurfb.2011.09.018

Author

Smith, M I. ; Foderà, Vito ; Sharp, James S ; Roberts, Clive J ; Donald, Athene M. / Factors affecting the formation of insulin amyloid spherulites. In: Colloids and Surfaces B: Biointerfaces. 2012 ; Vol. 89. pp. 216-22.

Bibtex

@article{70362080c6d140b0bda45d61090022a1,

title = "Factors affecting the formation of insulin amyloid spherulites",

abstract = "Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi-quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis, the effects of pH, temperature, salt, and protein concentration on spherulite formation were quantitatively determined for the first time. The number and size of spherulites measured with polarized light microscopy were related to changes in the colloidal stability of the solution and fibril nucleation times (measured by static light scattering). Importantly, changes in pH between 1.75 and 2 were found to result in a dramatic decrease in the spherulite radii, which were related to differences in the conformational stability of the protein. Moreover, estimates of the final spherulite volume fraction clearly indicate that amyloid spherulite formation is the dominant pathway for insulin aggregation in HCl solutions at low pH and protein concentrations below ~5 mg ml(-1), with the balance shifting towards fibrils as the concentration increases.",

author = "Smith, {M I.} and Vito Foder{\`a} and Sharp, {James S} and Roberts, {Clive J} and Donald, {Athene M}",

year = "2012",

month = jan,

day = "1",

doi = "10.1016/j.colsurfb.2011.09.018",

language = "English",

volume = "89",

pages = "216--22",

journal = "Colloids and Surfaces B: Biointerfaces",

issn = "0927-7765",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Factors affecting the formation of insulin amyloid spherulites

AU - Smith, M I.

AU - Foderà, Vito

AU - Sharp, James S

AU - Roberts, Clive J

AU - Donald, Athene M

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi-quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis, the effects of pH, temperature, salt, and protein concentration on spherulite formation were quantitatively determined for the first time. The number and size of spherulites measured with polarized light microscopy were related to changes in the colloidal stability of the solution and fibril nucleation times (measured by static light scattering). Importantly, changes in pH between 1.75 and 2 were found to result in a dramatic decrease in the spherulite radii, which were related to differences in the conformational stability of the protein. Moreover, estimates of the final spherulite volume fraction clearly indicate that amyloid spherulite formation is the dominant pathway for insulin aggregation in HCl solutions at low pH and protein concentrations below ~5 mg ml(-1), with the balance shifting towards fibrils as the concentration increases.

AB - Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi-quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis, the effects of pH, temperature, salt, and protein concentration on spherulite formation were quantitatively determined for the first time. The number and size of spherulites measured with polarized light microscopy were related to changes in the colloidal stability of the solution and fibril nucleation times (measured by static light scattering). Importantly, changes in pH between 1.75 and 2 were found to result in a dramatic decrease in the spherulite radii, which were related to differences in the conformational stability of the protein. Moreover, estimates of the final spherulite volume fraction clearly indicate that amyloid spherulite formation is the dominant pathway for insulin aggregation in HCl solutions at low pH and protein concentrations below ~5 mg ml(-1), with the balance shifting towards fibrils as the concentration increases.

U2 - 10.1016/j.colsurfb.2011.09.018

DO - 10.1016/j.colsurfb.2011.09.018

M3 - Journal article

C2 - 21982213

VL - 89

SP - 216

EP - 222

JO - Colloids and Surfaces B: Biointerfaces

JF - Colloids and Surfaces B: Biointerfaces

SN - 0927-7765

ER -

ID: 45803242

Department of Pharmacy