The role of the Nonlinear plastic response of fibrous networks for organoid growth

Branching morphogenesis is an essential process during organ development in all type of species, but the mechanisms governing its execution differ depending on cell types and extracellular matrices. An outstanding organ of interest to study branching morphogenesis is the human mammary gland since it undergoes most of its development postnatally during puberty. To mimic realistic conditions related to the human mammary gland we use a 3D organotypic collagen assay in which freshly isolated primary human mammary epithelial cells generate ductal structures with multiple branching points. We conducted long-term live-cell imaging over several days to reveal the dynamics of organoid formation. Extension of ducts correlated with large deformation of the surrounding matrix, imaged by tracking embedded fluorescent beads. We identify the hihlgy nonlinear plastic response of the collagen to govern the branching morphogenesis.