Mechanical plasticity of collagen directs branch elongation in human mammary gland organoids

Epithelial branch elongation is a central developmental process during branching morphogenesis in diverse organs. This fundamental growth process into large arborized epithelial networks is accompanied by structural reorganization of the surrounding extracellular matrix (ECM), well beyond its mechanical linear response regime. Here, we report that epithelial ductal elongation within human mammary organoid branches relies on the non-linear and plastic mechanical response of the surrounding collagen. Specifically, we demonstrate that collective back-and-forth motion of cells within the branches generates tension that is strong enough to induce a plastic reorganization of the surrounding collagen network which results in the formation of mechanically stable collagen cages. Such matrix encasing in turn directs further tension generation, branch outgrowth and plastic deformation of the matrix. The identified mechanical tension equilibrium sets a framework to understand how mechanical cues can direct ductal branch elongation.

Comparative toxicity assessment of nano- and bulk-phase titanium dioxide particles on the human mammary gland in vitro

There is a major concern that exposure to titanium dioxide (TiO2) nanoparticles (NPs) can have degrading effects on human health as well as mammary gland because of the increased use in numerous sorts of nanotech-based health care and food merchandise. Also, there is a scarcity in NP toxicity studies on the mammary gland; therefore, the aim of the present study was to compare toxicity caused by nano- and bulk-phase TiO2 particles on the human mammary gland in vitro. In comparison to bulk-TiO2 particles, nano-TiO2 cause a significant ( p < 0.05) reduction in viability and increased reactive oxygen species generation in the human mammary epithelial cells after a dose- (1, 2, 5, 10, 20, 50, and 100 µg/mL) and time (6, 12, 24, and 48 h)-dependent exposure. Further, an increase in genotoxicity in the mammary epithelial cells was observed as percent tail DNA and comet area was increased significantly ( p < 0.05) at 12 h of exposure (10 and 100 µg/mL) with nano-TiO2. The scanning electron microscopic examination showed that a 50 µg/mL dose of both nano-TiO2 and bulk-TiO2 particles cause morphological changes and retarded growth pattern of mammary epithelial cells at 12 h. Moreover, a significant ( p < 0.05) increase in apoptosis at 10 µg/mL and necrosis at 50 µg/mL concentrations of nano-TiO2 in comparison to bulk-TiO2 was observed in mammary epithelial cells. Finally, we can conclude that the toxicity caused by nano-TiO2 particles on the human mammary gland cells was comparatively higher than the bulk-TiO2 particles.