At the sub-micrometric scale, the meso-structure of clay matrix and its role in the thermo-hydro-mechanical (THM) behavior remains poorly known because this scale is hardly accessible to direct imaging. Based on a newly developed granular model, we study in this article the evolution of the meso-structure under mechanical and osmotic loadings. The model is a pure bottom-up approach coarse grained from molecular simulation results, which is quantitatively consistent with the usual THM behavior of clays. We focus on a few key features of the meso-structure: the degree of local anisotropy, the flexibility of the clay minerals, and the hydration states. It appears that at high confining pressures the meso-structure looses memory of its initial structure and the minerals exhibit a significant bending. The de-hydration, induced by mechanical or osmotic loading, is highly sensitive to the stress heterogeneities and thus to the loading history. A description of the heterogeneities at the meso-scale thus appears essential to the fine understanding of the THM behavior of clays.