Improving our knowledge about the structure of the casein micelle
Discovering the construction and transformation mechanisms of the casein micelle in order to understand its dynamicsThis protein aggregate, comparable to a sphere of a hundred nanometres in diameter, has been studied for the past thirty years using physico-chemical methods. However, its structure and thus its molecular and supramolecular organisation, are still poorly established. This lack of knowledge is a major conceptual obstacle for understanding and therefore controlling its functionalities. In fact, the casein micelle plays a key role in many transformation processes in the food industry.
A better understanding of casein micelle structureTo understand the micellar dynamics and organisation, we study the mechanisms of transport and construction of the micelle in the secretion pathway since these two processes are very closely interrelated. Our approach is unique in that we study these phenomena in situ in the mammary epithelial cell by exploiting the spatio-temporal aspect of micelle formation. The primary steps in the formation of the casein micelle are studied in vesicles derived from the rough endoplasmic reticulum, prepared from mammary tissues of rats or goats. These experiments reveal for the first time the existence of a form of alpha-S1 casein associated with the membrane in the endoplasmic reticulum and in the more distal compartments of the secretory pathway of mammary epithelial cells. Our data suggest that alpha-S1 casein, essential to the efficient export of other caseins from the endoplasmic reticulum to the Golgi apparatus, plays a key role in the first stages of the biogenesis of casein micelle and in the transport of caseins in the secretory pathway .
Through an approach that uses concentration by osmotic stress, a technique derived from "soft matter" physics, we showed that the micelle adopts a succession of behaviours typical of certain "model" colloids when the concentration is increased: hard sphere, "adhesive" sphere, followed by a "soft and deformable" colloid [2,3]. These results are directly applicable, through the knowledge of the concentration at the liquid-gel transition, for example. As a follow-up to this research, we explored the internal structure of the casein micelle by following its evolution during osmotic compression , using small angle x-ray scattering. During these manipulations, the physico-chemical environment of the micelle was unchanged, with the result that only its response to a mechanical stress was followed up.
The results obtained are particularly original and informative. They suggest that the micelle is a heterogeneous material consisting of dense regions that resist compression, and "soft" regions or voids that contract or cave in when the micelle is deformed (see illustration). This representation of a sponge-like casein micelle differs from existing models and is a major advance from the fundamental point of view.
Illustration: Structure of the casein micelle under osmotic compression: (A) SAXS spectra of the micelle at different casein concentrations. These spectra reveal three "oscillations", or characteristic distances, that correspond to the three levels of the internal structure of the micelle. (B) Representation of the internal structure: a sponge-like micelle with three structural levels.
Determining the role of alpha-S1 casein in the transport of caseins in the secretory pathway as well as in the formation of the casein micelle, and identifying the mechanisms responsible for the establishment and secretion of this supramolecular structure will allow us to better understand and, therefore, control casein micelle production by the mammary epithelial cell and the functionalities associated with it