Due to the high level of proline residue, casein molecules are able to form α-helix and β-sheet, which are essential factors for secondary protein structures [
11]. About 85% to 90% of casein in bovine milk exists in a colloidal form, known as micelles [
12,
13], which are porous, spherical aggregates with diameters ranging from 50 to 600 nm [
14,
15]. Various models of casein structure have been suggested [
6,
9,
12,
14,
16,
17]. It has been suggested that the integrity of the micelle is attributed to the hydrophobic interactions between casein molecules [
18], between caseins and calcium phosphate nano-clusters [
19], or between polymeric casein aggregates and casein-calcium phosphate aggregates [
20]. The structure of the casein micelle is still elusive, but the “hairy” layers of κ-casein on the surface of the micellar structure are generally accepted [
21,
22]. The casein micelle is extremely stable in heat treatment, due to the κ-casein layers [
12]. κ-casein is the only glycosylated casein with oligosaccharides attached to throline residues in the C-terminal, and the only calcium insensitive casein [
23]. The C-terminal, due to the increased hydrophilicity, is the “hairy” structure that extends into the serum solution, which contributes a stabilizing force [
23,
24]. During the production of cheese or rennet casein, chymosin is added to cut off the κ-casein tail, and the casein collapses to form a weak gel due to the loss of the inter-micellar repulsion force [
22]. That is why sweet whey protein (the whey produced from cheese making) contains a significant amount of Glycomacropeptide (GMP), which is one third of κ-casein (residues 106–169) and is present in whey protein products [
25]. The casein micelle is made up of 94% casein protein and 6% CCP [
26]. CCP stabilizes the casein micelle by crosslinking casein aggregates [
27,
28,
29,
30]. During acidification, such as using acid casein, in yogurt making, or in the natural milk-souring process, CCP is dissolved when the pH drops and causes a gradual dissolution of micellar integrity [
26,
28], and then casein starts to aggregate or precipitate.
The casein micelle is a very complex polymer aggregate, and interacts via hydrophobic and electrostatic interactions and calcium bridging [
31]. A typical casein micelle contains about 10,000 casein molecules [
11]. In the past, bovine casein molecule were usually called random coil protein because of the high content of proline residues, which prevents the formation of α-helix or β-sheet structures [
32,
33]. Casein has extreme heat stability and shows no evidence of denaturation to a more disordered structure [
34]. The term “rheomorphic” was also suggested for this type of protein [
35]. Caseins, considered rheomorphic proteins, have been adopted by many researchers [
36,
37,
38]. According to de Kruif and Holt’s definition, a rhomorphic protein is “one with an open conformation and therefore has a considerable degree of side chain, and possibly also backbone, conformational flexibility” [
5].