Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation.

ABSTRACT: Anchorage to a compliant extracellular matrix (ECM) and contact with neighboring cells impose important constraints on the proliferation of epithelial cells. How anchorage and contact dependence are inter-related and how cells weigh these adhesive cues alongside soluble growth factors to make a net cell cycle decision remain unclear. Here, we show that a moderate 4.5-fold stiffening of the matrix reduces the threshold amount of epidermal growth factor (EGF) needed to over-ride contact inhibition by over 100-fold. At EGF doses in the range of the dissociation constant (K(d)) for ligand binding, epithelial cells on soft matrices are contact inhibited with DNA synthesis restricted to the periphery of cell clusters. By contrast, on stiff substrates, even EGF doses at sub-K(d) levels over-ride

SUBMITTER: Kim JH 

PROVIDER: S-EPMC3065384 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature