In pure form, it is an amorphous white solid, tasteless and odourless, while its commercial type is yellowish with a pleasing odour. αS2‐Casein is least susceptible to aggregation because of alternating negatively charged and hydrophobic areas [68]. It is now widely known that milk is a complex biological fluid secreted by mammals whose most important biological function is to supply nutrients for the nourishment of the offspring. These submicelles were thought to be formed by the interaction of SH‐k‐casein monomers with those of αS‐ and β‐caseins as seen by analyzing concentration elution profiles. A brief summary of the various types of bonding forces responsible for the stabilization of protein structure will be discussed. αS1‐Casein has been shown to be present in bovine milk as αS1‐casein A‐D [71]. Another source of variability in caseins is genetic polymorphism. They used electron microscopy to study the ultrathin cross sections of embedded casein micelles and measured a diameter of 10 nm for the submicelles [24]. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. k‐casein, which is soluble over a very broad range of calcium ion concentrations unlike other forms of caseins like αS1‐, αS2‐, and β‐casein, is the fourth major component of the milk‐protein complex [69]. The individual families of casein proteins were identified by alkaline urea gel electrophoresis. The αS1‐ or ‐β‐caseins in their monomeric form with charged phosphate loops form limiting size aggregates/caseinate core. These results were confirmed by Buchheim and Welsch in 1973. Pepper and Farrell (1982) used gel chromatography to study interaction of concentration‐dependent interactions of EDTA dissociated whole‐casein micelles. The lack of phosphoserine cluster to bind calcium in k‐casein makes it to interact hydrophobically and act as a propagation terminator. Available from: From Structure to Biological Properties and Health Aspects, Biological Properties and Alternative Uses, Forces responsible for the stability of the casein micelle, Casein proteins as internally disordered calcium‐binding phosphoproteins, Properties and functions of different protein components of casein, Department of Clinical Biochemistry, University of Kashmir, Srinagar, J&K, India, Dr. B.R. It also includes active proteins providing antibodies, metal and vitamin‐binding proteins, and several protein hormones [2]. Due to the lack of well‐defined structure, crystallization of casein proteins to provide a three‐dimensional crystal structure is not possible, but at the other end, this lack of structure helps to facilitate proteolysis and therefore ready absorption of amino acids and small peptides in the intestine [2, 78]. According to this model, hydrophobic interaction is the driving force for the formation of casein micelles and electrostatic repulsions are responsible for limiting the growth of polymers [36]. Sedimentation velocity experiments performed by Waugh et al., in 1971, demonstrated that αS1‐ and k‐casein complexes can be reformed from already isolated fractions [40]. Some of the proteins are involved in calcium phosphate transport while others in stability of other caseins and micelle. Carroll and Farrell in 1983 also found that the location of k‐casein is indeed related to casein micelle size using ferritin‐labeled double‐antibody technique coupled with electron microscopy [33]. There are 10 different molecular forms of k‐casein on the basis of degree of glycosylation and is the only casein which is glycosylated [56, 70, 71]. The purpose of a micelle is to make large insoluble molecules soluble in water. According to this model, three chains of αS1‐ and β‐casein are linked to the trimers of k‐casein which radiate from the k‐casein node which is present as a Y‐like structure. When consumed, the casein micelle is disrupted by acid in the stomach, which forms a clot and allows the slow breakdown of the protein and, therefore, a sustained supply of amino acids over several hours, allowing the body to retain and use those amino acids more effectively. αS1‐, αS2‐, and β‐casein precipitate when calcium binds to their phosphoserine residues. It stabilizes micelle formation thereby prevent precipitation of casein in milk. This model describes the micelle core as a scaffold of colloidal calcium phosphate and αS1‐caseins, while β‐caseins are held by hydrophobic interactions. The last casein sequenced was αS2‐casein which possesses most unique primary structure of all the caseins with a molecular weight of 25,150 [67]. Casein proteins provide one of the best example of intrinsically disordered or natively disordered or natively unfolded proteins [57]. The second most abundant milk protein is β‐casein with five phosphoserine residues and a molecular weight of 23,980 [65]. This actually contains two diametrically opposite theories. Open Access is an initiative that aims to make scientific research freely available to all. According to model proposed by Holt, the casein micelle forms a tangled web of flexible casein networks forming a gel‐like structure with C‐terminal region of k‐casein extending to form a hairy layer and microgranules of colloidal calcium phosphate at center. The model assigns no role to calcium caseinate interactions and ignores the role of colloidal calcium phosphate involvement in stabilization of the micelle. Hydrophobic interactions between the constituent proteins and the calcium phosphate linkages keep the submicelle together. Casein proteins belong to one of the larger family of secretory calcium‐binding phosphoproteins as has been found by the analysis of structure of human genome. Each of these calcium caseinate complex units is probably composed of an inner core consisting of a αS1‐ and β‐casein, surrounded by an outer layer rich in αS1‐ and k‐casein, as suggested by Waugh and noble [14, 25]. Disulfide bonds between cysteine residues during folding of pleated sheet structures, helical segments, and unordered structures leads to the formation of tertiary structure. Mammalian milk is a complex fluid mixture of various proteins, minerals, and lipids, which play an important role in providing nutrition and immunity to the newborn. The rest of proteins found in milk are trace fractions of glycoprotein [6]. Hydrogen bonds between the various components of casein during the formation of highly aggregated casein micelle are possible but in case of ionizable side chains of monomeric proteins which are accessible to water, their contribution to the stability of these monomeric proteins is very less. © Copyright 2020 Hearst Communications, Inc. αS1‐Casein plays an important role in the ability of milk to transport calcium phosphate. Built by scientists, for scientists. k‐casein contains only one or two phosphoseryl residues and is only casein which is glycosylated [53]. In addition to their biological role, which is to provide nutrition, caseins are also studied for their role in human health and other malfunctions such as stone‐forming diseases in bovine animals [9–12]. Each of the four different caseins may have a variety of numbers of phosphate groups attached through their serine or threonine residues. Since these are among the most hydrophobic proteins, role of hydrophobic bonding in the stabilization of casein cannot be ignored. The casein micelle is the centerpiece to the many functions of casein. According to this model of casein micelle, the surface of the micelle comprises αS1‐ and β‐caseins with some colloidal calcium phosphate [18]. The structure and properties of casein micelle as a whole and individual casein proteins, which constitute the micelle, are discussed.