Structure of biomimetic casein micelles: critical tests of the hydrophobic colloid and multivalent-binding models using recombinant deuterated and phosphorylated β-casein

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dc.contributor.authorRaynes, JKen_AU
dc.contributor.authorMata, JPen_AU
dc.contributor.authorWilde, KLen_AU
dc.contributor.authorKelly, SMen_AU
dc.contributor.authorHolt, Cen_AU
dc.date.accessioned2024-01-11T23:36:53Zen_AU
dc.date.available2024-01-11T23:36:53Zen_AU
dc.date.issued2023-10-24en_AU
dc.date.statistics2023-12-01en_AU
dc.description.abstractMilk contains high concentrations of amyloidogenic casein proteins and is supersaturated with respect to crystalline calcium phosphates such as apatite. Nevertheless, the mammary gland normally remains unmineralized and free of amyloid. Unlike κ-casein, β- and αS-caseins are highly effective mineral chaperones that prevent ectopic and pathological calcification of the mammary gland. Milk invariably contains a mixture of two to five different caseins that act on each other as molecular chaperones. Instead of forming amyloid fibrils, several thousand caseins and hundreds of nanoclusters of amorphous calcium phosphate combine to form fuzzy complexes called casein micelles. To understand the biological functions of the casein micelle its structure needs to be understood better than at present. The location in micelles of the highly amyloidogenic k-casein is disputed. In traditional hydrophobic colloid models, it, alone, forms a stabilizing surface coat that also determines the average size of the micelles. In the recent multivalent-binding model, κ-casein is present throughout the micelle, in intimate contact with the other caseins. To discriminate between these models, a range of biomimetic micelles was prepared using a fixed concentration of the mineral chaperone b-casein and nanoclusters of calcium phosphate, with variable concentrations of κ-casein. A biomimetic micelle was also prepared using a highly deuterated and in vivo phosphorylated recombinant β-casein with calcium phosphate and unlabelled κ-casein. Neutron and X-ray scattering experiments revealed that κ-casein is distributed throughout the micelle, in quantitative agreement with the multivalent-binding model but contrary to the hydrophobic colloid models. © 2023 The Authorsen_AU
dc.description.sponsorshipWe thank Dr Tom Nebl from CSIRO Manufacturing for the mass spectrometry analysis and the late Prof. John W. White, The Australian National University, for his guidance during the SANS experiments. E. M. Little and J. G. Grossmann are thanked for their expert help in preparing and characterising samples by SAXS. This work was supported by the Australian Synchrotron proposal P9858, and ANSTO SANS and deuteration facility proposals P4288, P6146, NDF2878, NDF3516, NDF3915 and NDF5725.en_AU
dc.identifier.articlenumber4608131en_AU
dc.identifier.citationRaynes, J. K., Mata, J., Wilde, K. L., Kelly, S. M., & Holt, C. Structure of biomimetic casein micelles: critical tests of the hydrophobic colloid and multivalent-binding models using recombinant deuterated and phosphorylated β-casein. Preprint, SSRN 4608131. doi:10.2139/ssrn.4608131en_AU
dc.identifier.journaltitleSSRNen_AU
dc.identifier.urihttps://papers.ssrn.com/sol3/papers.cfm?abstract_id=4608131en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15331en_AU
dc.language.isoenen_AU
dc.publisherSSRNen_AU
dc.relation.urihttps://doi.org/10.2139/ssrn.4608131en_AU
dc.subjectCaseinen_AU
dc.subjectMineralsen_AU
dc.subjectCalcium phosphatesen_AU
dc.subjectSmall angle scatteringen_AU
dc.subjectProteinsen_AU
dc.subjectColloidsen_AU
dc.subjectValenceen_AU
dc.titleStructure of biomimetic casein micelles: critical tests of the hydrophobic colloid and multivalent-binding models using recombinant deuterated and phosphorylated β-caseinen_AU
dc.typeJournal Articleen_AU
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