Simulating the self-association of caseins: Towards a model for the casein micelle

A Monte Carlo computer simulation is used to simulate the self-association of model casein-like block copolymers. One-component studies of as1 and casein show a strong tendency to form large micelles, with some evidence of flower-like and worm-like micelles in as1-casein systems. as2-Casein forms small micelles in a one-component system, and has difficulty forming mixed micelles in binary and three-component mixtures. This is attributed to its tetra-block structure (alternating hydrophobic and hydrophilic blocks), where one of the hydrophobic blocks is attached at both ends to a hydrophilic block, which reduces its ability to self-associate with other hydrophobic blocks. The order of increasing micelle size depends on whether hydrophobic association is allowed between blocks on the same chain or not. When allowed, the chains tend to fold up on themselves which makes micellization more difficult. The order of increasing micelle size is then as2 .as1. If intra-chain hydrophobic association is not allowed (increased rigidity of the blocks) the order of increasing micelle size changes to as2 as1. In the latter case two hydrophobic blocks at the ends of the as1-chain are able to associate with more than one hydrophobic micellar core, and thus act as a bridge between two micelles. In binary systems only as1 + casein mixtures show a strong preference to form micelles where the hydrophobic blocks of the two chains are mixed relatively evenly in the hydrophobic core, with an approximate 1:1 ratio of the two chains. When as2-casein is present in the binary simulations it dominates the micellization behavior by limiting the growth of micelles. This is most likely due to the second hydrophobic block of as2-chains having a low propensity to associate with other hydrophobic blocks, and thus having a low ability to propagate micelle growth. A similar situation is seen in three component mixtures of as1 + as2 + at ratios of 1:1:1 and 4:1:4.