Interactions between cells and the extracellular matrix (ECM) generate two classes of signals, mechanical and biochemical. In the case of the mammary epithelial cell, both are required to initiate ECM-dependent expression of the abundant milk protein beta-casein. Mechanical signals induce a cellular rounding, while functional biochemical signals are associated with an increase in tyrosine phosphorylation. These individual components are part of a complex signalling hierarchy that leads to the emergence of the fully functional lactational phenotype. Interestingly, both the assembly and disassembly of this hierarchy, which occur cyclically in vivo, are constantly modulated by dynamic and reciprocal interactions that take place within a functional unit composed of both the cell and the ECM.