Figure 2. Tissue forces in mammary gland development and function.

The mammary gland is subjected to a number of biophysical forces (red arrows) that facilitate its development and function. a, During puberty, branching is marked by the ductal outgrowth of the mammary epithelium into the adipocyte-rich (yellow) stroma of the fat pad by directing the collective migration of mammary epithelial cells (MEC) led by the terminal end bud (TEB). Branch orientation is regulated by the bundling of type I collagen fibers (grey) proximal to the TEB. b, The developed breast ducts comprise an inner layer of oriented luminal epithelial cells (green) and an outer layer of contractile myoepithelial cells (pink). c, During pregnancy, hormonal cues direct the expansion of alveolar cells that mature into milk-secreting cells. The alveoli expand out from the ducts filling the majority of the fat pad and the stroma is remodeled to accommodate the expanding epithelium. d, During lactation, the accumulation of milk and distension of ducts applies compressive stress on the surrounding cells and basement membrane. Upon suckling-mediated oxytocin stimulation, epithelial cells encounter inward tensile stress and the myoepithelium contracts to force milk out of the alveolar sacs. e, During involution, the mammary gland undergoes extensive remodeling of the cellular and extracellular stroma to the pre-pregnancy architecture. The remodeled stroma in these stages consequently alters the signals and forces encountered by MECs within the ducts and by doing so, sets the stage for subsequent cycles of proliferation, differentiation or involution.