Casein Micelle Structure, Functions, and Interactions



Casein micelles are supramolecule of colloidal size. They are modeled as having a lattice structure in which both casein-calcium phosphate aggregates and casein polymer chains act together to maintain its supramolecular integrity. The interlocked structure and occurrence of multiple interactions produce an open sponge-like particle that is generally resistant to spatial changes. The structural arrangement within the casein supramolecule can be modified by environmental changes that modify hydrophobic interactions and calcium phosphate solubility. This is discussed in relation to microstructure imaging using electron microscopy and changes that occur during acid coagulation, heating, and ethanol addition.


  1. Anema, S.G. and Klostermeyer, H. (1997). Heat-induced, pH-dependent dissociation of casein micelles on heating reconstituted skim milk at temperatures below 100°C. J. Agric. Food Chem. 45, 1108–1115.Google Scholar
  2. Anema, S.G. and Li, Y. (2003). Effect of pH on the association of denatured whey proteins with casein micelles in heated reconstituted skim milk. J. Agric. Food Chem. 51, 1640–1646.Google Scholar
  3. Aoki, T., Kako, Y. and Imamura, T. (1986). Separation of casein aggregates cross-linked by colloidal calcium phosphate from bovine casein micelles by high performance gel chromatography in the presence of urea. J. Dairy Res. 53, 53–59.Google Scholar
  4. Aoki, T., Umeda, T. and Kako, Y. (1992). The least number of phosphate groups for crosslinking of casein by colloidal calcium phosphate. J. Dairy Sci. 75, 971–975.Google Scholar
  5. Aoki, T., Yamada, N., Kako, Y. and Imamura, T. (1988). Dissociation during dialysis of casein aggregates cross-linked by colloidal calcium phosphate in bovine casein micelles. J. Dairy Res. 55, 189–195.Google Scholar
  6. Bloomfield, V.A. (1979). Association of proteins. J. Dairy Res. 46, 241–252.Google Scholar
  7. Bloomfield, V.A. and Mead, R.J., Jr. (1975). Structure and stability of casein micelles. J. Dairy Sci. 58, 592–601.Google Scholar
  8. Bloomfield, V.A. and Morr, C.V. (1973). Structure of casein micelles: physical methods. Neth. Milk Dairy J. 27, 103–120.Google Scholar
  9. Bylund, G. et al. (2003). Dairy Processing Handbook, 2nd edn., Tetra Pak Processing Systems AB, Lund, Sweden.Google Scholar
  10. Corredig, M. and Dalgleish, D.G. (1996). The binding of α-lactalbumin and β-lactoglobulin to casein micelles in milk treated by different heating systems. Milchwissenschaft 51, 123–127.Google Scholar
  11. Dalgleish, D.G. (2011). On the structural models of bovine casein micelles–review and possible improvements. Soft Matter 7, 2265–2272.Google Scholar
  12. Dalgleish, D.G. and Law, A.J.R. (1988). pH-induced dissociation of bovine casein micelles. I. Analysis of liberated caseins. J. Dairy Res. 55, 529–538.Google Scholar
  13. Dalgleish, D.G. and Parker, T. G. (1979). Quantitation of αS1-casein aggregation by the use of polyfunctional models. J. Dairy Res. 46, 259–263.Google Scholar
  14. Dalgleish, D.G., Spagnuolo, P.A. and Goff, H.D. (2004). A possible structure of the casein micelle based on high-resolution scanning electron microscopy. Int. Dairy J. 14, 1025–1031.Google Scholar
  15. Davies, F.L., Shankar, P.A. and Brooker, B.E. (1977). A heat-induced change in the ultrastructure of milk and its effect on gel formation in yoghurt. J. Dairy Res. 45, 53–58.Google Scholar
  16. de Kruif, C.G. (1998). Supra-aggregates of casein micelles as a prelude to coagulation. J. Dairy Sci. 81, 3019–3028.Google Scholar
  17. de Kruif, C.G. and Holt, C. (2003). Casein micelle structure, functions, and interactions, in, Advanced Dairy Chemistry Proteins, 3rd edn., Vol. 1A, P.F. Fox and P.L.H. McSweeney, eds., Kluwer Academic/Plenum Publishers, New York. pp. 233–270.Google Scholar
  18. Dickinson, E. and Matsumura, Y. (1991). Time-dependent polymerization of β-lactoglobulin through disulfide bonds at the oil-water interface in emulsions. Int. J. Biol. Macromolecules 13, 26–30.Google Scholar
  19. Dosako, S., Kaminogawa, S., Taneya, S. and Yanauchi, K. (1980). Hydrophobic surface areas and net charge of αs1-, κ-casein and αs1-casein:κ -casein complex. J. Dairy Res. 47, 123–137.Google Scholar
  20. Euston, S.R. and Horne, D.S. (2005). Simulating the self-association of caseins. Food Hydrocolloids 19, 379–386.Google Scholar
  21. Farrell, H.M., Jr. (1973). Models for casein micelle formation. J. Dairy Sci. 56, 1195–1206.Google Scholar
  22. Farrell, H.M., Jr., Brown, E.M., Hoagland, P.D. and Malin, E. L. (2003). Higher order structures of caseins: a paradox, in, Advanced Dairy Chemistry Proteins, 3rd edn., Vol. 1A, P.F. Fox and P.L.H. McSweeney, eds., Kluwer Academic/Plenum Publishers, New York. pp. 203–232.Google Scholar
  23. Farrer, D. and Lips, A. (1999). On the self-assembly of sodium caseinate. Int. Dairy J. 9, 281–286.Google Scholar
  24. Farrell, H.M., Jr., Malin, E.L., Brown, E.M. and Qi, P.X. (2006a). Casein micelle structure: what can be learned from milk synthesis and structural biology? Curr. Opin. Colloid Interface Sci. 11, 135–147.Google Scholar
  25. Farrell, H.M., Jr., Qi, P.X. and Uversky, V.N. (2006b). New views of protein structure: applications to the caseins: protein structure and functionality, in, Advances in Biopolymers: Molecules, Clusters, Networks, and Interactions. M.L. Fishman, P.X. Qi, and L. Wisker, eds., Am. Chem. Soc., Washington. pp. 52–70.Google Scholar
  26. Garnier, J. (1973). Models of casein micelle structure. Neth. Milk Dairy J. 27, 240–248.Google Scholar
  27. Garnier, J. and Ribadeau-Dumas, B. (1970). Structure of the casein micelle: a proposed model. J. Dairy Res. 37,493–504.Google Scholar
  28. Garnier, J., Yon, J. and Mocquot, G. (1964). Contribution to the study of the association between κ- and αs-caseins at neutral pH. Biochimica et Biophyica. Acta 82, 481–493.Google Scholar
  29. Gebhardt, R., Takeda, N., Kulozik, U. and Doster, W. (2011). Structure and stabilizing interactions of casein micelles probed by high-pressure light scattering and FTIR. J. Phys. Chem. B. 115, 349–2359.Google Scholar
  30. Heertje, I., Visser, J. and Smits, P. (1985). Structure formation in acid milk gels. Food Microstruct. 4, 267–278.Google Scholar
  31. Helminen, H.J. and Ericsson, J.L.E. (1968). Studies on mammary gland involution. 1. On the ultrastructure of the lactating mammary gland. J. Ultrastruct. Res. 25, 193–213Google Scholar
  32. Hojou, K., Oikawa, T., Kanaya, K., Kimura, T., and Adachi, K. (1977). Some applications of ion beam sputtering to high resolution electron microscopy. Micron 8, 151–170.Google Scholar
  33. Holt, C. (1992). Structure and stability of bovine casein micelles. Adv. Prot. Chem. 43, 63–151.Google Scholar
  34. Holt, C. (1998). Casein micelle substructure and calcium phosphate interactions studied by sephacryl column chromatography. J. Dairy Sci. 81, 2994–3003.Google Scholar
  35. Holt, C. and Horne, D.S. (1996). The hairy casein micelle: evolution of the concept and its implications for dairy technology. Neth. Milk Dairy J. 50, 85–111.Google Scholar
  36. Holt, C. and Sawyer, L. (1993). Caseins as rheomorphic proteins: interpretation of the primary and secondary structures of the αs1-, β-, and κ-caseins. J. Chem. Soc. Faraday Trans. 89, 2683–2692.Google Scholar
  37. Holt, C., Davies, D.T. and Law, A.J.R. (1986). Effects of colloidal calcium phosphate content and free calcium ion concentration in the milk serum on the dissociation of bovine casein micelles. J. Dairy Res. 53, 557–572.Google Scholar
  38. Holt, C., de Kruif, C.G., Tunier, R. and Timmons, P.A. (2003). Substructure of bovine casein micelles by small angle X-ray and neutron scattering. Colloids Surf. A 213, 275–284.Google Scholar
  39. Holt, C., Wahlgren, N.M. and Drakenberg, T. (1996). Ability of a β-CN phosphopeptide to modulate the precipitation of calcium phosphate by forming amorphous dicalcium phosphate nanoclusters. Biochem. J. 314, 1035–1039.Google Scholar
  40. Holt, C., Timmis, P.A., Errington, N. and Leaver, J. (1998). A core-shell model of calcium phosphate nanoclusters stabilized by β− casein phosphopeptides, derived from sedimentation equilibrium and small-angle X-ray and neutron-scattering measurements. Eur. J. Biochem. 252, 73–78.Google Scholar
  41. Horne, D.S. (1986). Steric stabilization and casein micelle stability. J. Coll. Interf. Sci. 111, 250–260.Google Scholar
  42. Horne, D.S. (1992) Alcohol stability, in, Advanced Dairy Chemistry Proteins, 2nd edn., Vol. 1, P.F. Fox, ed., Elsevier Applied Science, New York. pp. 657–589.Google Scholar
  43. Horne, D.S. (1998). Casein interactions: casting light on the black boxes, the structure of dairy products. Int. Dairy J. 8, 171–177.Google Scholar
  44. Horne, D.S. (2002a). Casein structure, self assembly and gelation. Curr. Opin. Coll. Interf. Sci. 7, 456–461.Google Scholar
  45. Horne, D.S. (2002b). Caseins, micellar structure, in, Encyclopaedia of Dairy Sciences, Vol. 3, R. Roginski, P.F. Fox and J.W Fuquay, eds., Academic Press, NY. pp. 1902–1909.Google Scholar
  46. Horne, D.S. (2006). Casein micelle structure: models and muddles. Curr. Opin. Coll. Interf. Sci. 11, 148–153.Google Scholar
  47. Horne, D.S. and Davidson, C.M. (1987). Alcohol stability of bovine skim-milk. Anomalous effects with trifluoroethanol. Milchwissenschaft 42, 509–512.Google Scholar
  48. Horne, D.S., Parker, T.G. and Dalgleish, D.G. (1988). Casein micelles, polycondensation, and fractals, in, Food Colloids, R.D. Bee, P. Richmond and J. Mingins, eds, Royal Soc. Chem., London. pp. 400–406.Google Scholar
  49. Kalab, M., Emmons, D.B., and Sargant, A.G. (1976). Milk gel structure: V. Microstructure of yoghurt as related to the heating of milk. Milchwissenschaft 31, 402–408.Google Scholar
  50. Karlsson, A., Ipsen, R. and Ardö, Y. (2007). Observations of casein micelles in skim milk concentrate by transmission electron microscopy. LWT-Food Sci. Technol. 40, 1102–1107.Google Scholar
  51. Kim, B.Y. and Kinsella, J.E. (1989). Effect of temperature and pH on the coagulation of casein. Milchwissenschaft 44, 622–625.Google Scholar
  52. Kirchmeuer, O. (1973). Arrangement of components, electrical charge and interaction energies of casein micelles. Neth. Milk Dairy J. 27, 191–198.Google Scholar
  53. Knoop, A.M., Knoop, E. and Wiechen, A. (1979). Sub-structure of synthetic casein micelles. J. Dairy Res. 46, 357–350.Google Scholar
  54. Kumosinski, T.P., Pessen, H., Farrell, H.M., Jr. and Brumberger, H. (1988). Determination of the quaternary structure of bovine caseins by small-angle X-ray scattering. Arch. Biochem. Biophys. 266, 548–561.Google Scholar
  55. Lin, S.H.C., Leong, L.S., Dewan, R.K., Bloomfield, V.A. and Morr, C.V. (1972). Effect of calcium ion on the structure of native bovine casein micelles. Biochem. 11, 1818–1821.Google Scholar
  56. Linderstrøm Lang, K. (1929). Studies on casein. III. On the fractionation of casein. Compt. Rend. Trav. Lab. Carlsberg. 36(9), 1.Google Scholar
  57. Lucey, J. A. (2002). Formation and physical properties of milk protein gels. J. Dairy Sci. 85, 281–294.Google Scholar
  58. Malin, E.L., Brown, E.M., Wickham, E.D. and Farrell, H.M., Jr. (2005). Contributions of terminal peptides to the associative behavior of αs1-casein. J. Dairy Sci. 88, 2318–2328.Google Scholar
  59. Marchin, S., Putaux, J.-L., Pignon, F. and Léonil, J. (2007). Effects of the environmental factors on the casein micelle structure studied by cryo transmission electron microscopy and small-angle X-ray scattering/ultrasmall-angle X-ray scattering. J. Chem. Phys. 126(4), 045101 (1–10).Google Scholar
  60. McMahon, D.J. and Brown, R.J. (1984). Composition, structure, and integrity of casein micelles: a review. J. Dairy Sci. 67, 499–512.Google Scholar
  61. McMahon, D.J. and McManus, W.R. (1998). Rethinking casein micelle structure using electron microscopy. J. Dairy Sci. 81, 2985–2993.Google Scholar
  62. McMahon, D.J. and Oommen, B.S. (2008). Supramolecular structure of the casein micelle. J. Dairy Sci. 91, 1709–1721.Google Scholar
  63. McMahon, D.J., Du, H., McManus, W.R. and Larsen, K.M. (2009). Microstructural changes in casein supramolecules during acidification of skim milk. J. Dairy Sci. 92, 5854–5867.Google Scholar
  64. Meyer, J.L. and Angino, E.E. (1977). The role of trace metals in calcium urolithiasis. Invest. Urol. 14, 347–350.Google Scholar
  65. Morr, C.V. (1967). Effect of oxalate and urea upon ultracentrifugation properties of raw and heated skim milk casein micelles. J. Dairy Sci. 50, 1744–1751.Google Scholar
  66. O’Connell, J.E., Kelly, A.L., Auty, M.A.E., Fox, P.F. and de Kruif, C.G. (2001a). Ethanol-dependent temperature-induced dissociation of casein micelles. J. Agric. Food Chem. 49, 4420–4423.Google Scholar
  67. O’Connell, J.E., Kelly, A.L., Fox, P.F. and de Kruif, C.G. (2001b). Mechanism for the ethanol-dependent heat-induced dissociation of casein micelles. J. Agric. Food Chem. 49, 4424–4428.Google Scholar
  68. Oommen, B.S. (2004). Casein Supramolecules: Structure and Coagulation Properties, Ph.D. Dissertation, Utah State University, Logan, UT, USA.Google Scholar
  69. Payens, T.A.J. (1966). Association of caseins and their possible relation to structure of the casein micelle. J. Dairy Sci. 49, 1317–1324.Google Scholar
  70. Payens, T.A.J. (1968). Self association and complex formation of αs1- and β-caseins. Biochemical J. 108, 14p.Google Scholar
  71. Payens, T.A.J. and Markwijk, V. (1963). Some features of the association of β-casein. Biochimi. Biophys. Acta 71, 517–530.Google Scholar
  72. Payens, T.A.J. and Vreeman, H.J. (1982). Casein micelles and micelles of κ- and β-casein, in, Solution Behavior of Surfactants: Theoretical and Applied Aspects, K.L. Mittal and E.J. Fendler, eds., Vol. 1, Perseus Publishing, Cambridge, MA. pp. 543–571.Google Scholar
  73. Pessen, H., Kumosinski, T.F. and Farrell, H.M., Jr. (1989). Small-angle x-ray scattering investigation of the micellar and submicellar forms of bovine casein. J. Dairy Res. 56, 443–451.Google Scholar
  74. Pierre, A. and Brule, G. (1981). Mineral and protein equilibria between the colloidal and soluble phases of milk at low temperature. J. Dairy Res. 48, 417–428.Google Scholar
  75. Pierre, A., Brule, G. and Fauquant, J. (1983). Etude de la mobilite du calcium dans le lait a l’aide du calcium. Lait. 63, 473–489.Google Scholar
  76. Pignon, F., Belina, G., Narayanan, T., Paubel, X., Magnin, A. and Gésan-Guiziou, G. (2004). Structure and rheological behavior of casein micelle suspensions during ultrafiltration process. J. Chem. Phys. A 121, 8138–8146.Google Scholar
  77. Rasmussen, L.K., Johnsen, L.B., Tsiora, A., Sørenson, E.S., Thomsen, J.K., Nielsen, N.C., Jakobsen, H.J. and Petersen, T.E. (1999). Disulphide-linked caseins and casein micelles. Int. Dairy J. 9, 215–218.Google Scholar
  78. Roefs, S.P.F.M., Walstra, P., Dalgleish, D.G. and Horne, D.S. (1985). Preliminary note on the change in casein micelles caused by acidification. Neth. Milk Dairy J. 39, 119–122.Google Scholar
  79. Rollema, H.S. (1992). Chemistry of milk proteins, in, Developments in Dairy Chemistry Proteins, Vol. 1, P.F. Fox, ed., Applied Science, London. pp. 111–140.Google Scholar
  80. Rollema, H.S. and Brinkhuis, J.A. (1989). A 1H-NMR study of bovine casein micelles; influence of pH, temperature and calcium ions on micellar structure. J. Dairy Res. 56, 417–425.Google Scholar
  81. Rose, D. (1969). A proposed model of micelle structure in bovine milk. Dairy Sci. Abstr. 31, 171–175.Google Scholar
  82. Schmidt, D.G. (1980). Colloidal aspects of casein. Neth. Milk Dairy J. 34, 42–64.Google Scholar
  83. Schmidt, D.G. and Payens, T.A.J. (1976). Micellar aspects of casein, in, Surface and Colloid Science, Vol. 9, E. Matijevic, ed., Wiley-Interscience, New York. pp. 165–229.Google Scholar
  84. Schmidt, D.G., Koops, J. and Westerbeek, D. (1977). Properties of artificial casein micelles. 1). Preparation, size distribution and composition. Neth. Milk Dairy J. 31, 328–341.Google Scholar
  85. Schmidt, D.G., van der Spek, C.A., Buchheim, W. and Hinz, A. (1974). On the formation of artificial casein micelles. Milchwissenschaft 29, 455–459.Google Scholar
  86. Schmidt, D.G., Walstra, P. and Buchheim, W. (1973). The size distribution of casein micelles in cow’s milk. Neth. Milk Dairy J. 27, 128.Google Scholar
  87. Singh, H., Roberts, M.S., Munro, R.A. and Teo, C.T. (1996a). Acid-induced dissociation of casein micelles in milk: effects of heat treatment. J. Dairy Sci. 79, 1340–1346.Google Scholar
  88. Singh, H., Sharma, R., Taylor, M.W. and Creamer, L.K. (1996b). Heat-induced aggregation and dissociation of protein and fat particles in recombined milk. Neth. Milk Dairy J. 50, 149–166.Google Scholar
  89. Slattery, C.W. (1976). Review: casein micelle structure; an examination of models. J. Dairy Sci. 59, 1547–1556.Google Scholar
  90. Slattery, C.W. (1979). A phosphate-induced sub-micelle equilibrium in reconstituted casein micelle systems. J. Dairy Res. 46, 253–258.Google Scholar
  91. Slattery, C.W. and Evard, R. (1973). A model for the formation and structure of casein micelles from subunits of variable composition. Biochim. Biophys. Acta. 317, 529–538.Google Scholar
  92. Smith, E., Clegg, R. and Holt, C. (2004). A biological perspective on the structure and function of caseins and casein micelles. Int. J. Dairy Technol. 57, 121–126.Google Scholar
  93. Snøeren, T.H.M., Klok, H.J., van Hooydonk, A.C.M. and Dammam, A.J. (1984). The voluminosity of casein micelles. Milchwissenschaft 39, 461–463.Google Scholar
  94. Swaisgood, H.E. (1992). Chemistry of the caseins, in, Advanced Dairy Chemistry Proteins, 3rd edn., Vol. 1A, P.F. Fox and P.L.H. McSweeney, eds., Kluwer Academic/Plenum Publishers, New York. pp. 63–110.Google Scholar
  95. Swaisgood, H.E. (2003). Chemistry of the caseins, in, Advanced Dairy Chemistry Proteins, Vol 1A, P.F. Fox and P.L.H. McSweeney, eds., Kluwer Academic/Plenum Publishers, New York. pp. 139–187.Google Scholar
  96. Swaisgood, H.E. and Brunner, J.R. (1973). The caseins. CRC Crit. Rev. Food Technol. 3, 375–414.Google Scholar
  97. Thompson, M.P., and Farrell, H.M., Jr. (1973). The casein micelle-the forces contributing to its integrity. Neth. Milk Dairy J. 27, 220–239.Google Scholar
  98. Thurn, A., Buchard, W. and Niki R. (1987). Structure of casein micelles 2. as1-. Coll. Poylmer Sci. 265, 653–666.Google Scholar
  99. Trejo, R., Dokland, T., Jurat-Fuentes, J. and Harte, F. (2011). Cryo-transmission electron tomography of native milk casein micelles. J. Dairy Sci. 94, 5770–5775.Google Scholar
  100. Tuiner, R. and de Kruif, C.G. (2002). Stability of casein micelles in milk. J. Chem. Phys. 117, 1290–1295.Google Scholar
  101. Udabage, P., McKinnon, I.R. and Augustin, M.A. (2003). The use of sedimentation field flow fractionation and photon correlation spectroscopy in the characterization of casein micelles. J. Dairy Res. 70, 453–459Google Scholar
  102. van Hooydonk, A.C.M., Boerrigter, I.J. and Hagedoorn, H.G. (1986). pH-induced physico-chemical changes of casein micelles in milk and their effect on renneting: 2. Effect of pH on renneting of milk. Neth. Milk Dairy J. 40, 297–313.Google Scholar
  103. Walstra, P. (1990). On casein micelles. J. Dairy Sci. 73, 1965–1979.Google Scholar
  104. Walstra, P. (1999). Casein sub-micelles: do they exist? Int. Dairy. J. 9, 189–192.Google Scholar
  105. Waugh, D.F. and Noble, R.W. (1965). Casein micelles: formation and structure. J. Am. Chem. Soc. 78, 2246–2257.Google Scholar
  106. Yoshikawa, M., Sasaki, R. and Chiba, H. (1981). Effects of chemical phosphorylation of bovine casein components on the properties related to casein micelle formation. Agric. Biol. Chem. 45, 909–914.Google Scholar
  107. Zadow, J.G. (1993). Alcohol-mediated temperature-induced reversible dissociation of the casein micelle in milk. Aust. J. Dairy Technol. 48, 78–81.Google Scholar
  108. Zhang, Z.P., Fujii, M. and Aoki, T. (1996). Behavior of calcium and phosphate in artificial casein micelles. J. Dairy Sci. 79, 1722–1727.Google Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Western Dairy CenterUtah State UniversityLoganUSA
  2. 2.Glanbia Nutritionals ResearchTwin FallsUSA

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