The Effect of Viscoelastic Substrates on Epithelial-Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a significant process that occurs in fibrosis and cancer progression. During EMT, cells exhibit changes in morphology and gene expression which promote cell motility. Elucidating the chemical and mechanical factors that regulate this process can lead to a better understanding of how cancer progresses and spreads throughout the body. Previous experiments have shown that increasing stiffness of the extracellular matrix promotes EMT. However, tissues within the body display viscoelastic properties, and how matrix viscoelasticity impacts EMT is not clear. For this study, viscoelastic hydrogels mimicking the mechanical properties of healthy and tumorigenic breast tissue were synthesized and characterized. Cells cultured on elastic hydrogels exhibited EMT-associated changes in cell shape, cell aspect ratio and gene expression in response to transforming growth factor (TGF)-β1. In contrast, cells cultured on viscoelastic hydrogels were refractive to TGFβ1-induced morphology and gene expression changes. Immunofluorescence staining revealed that cleaved caspase 3, a marker of apoptosis, increased in cells cultured on viscoelastic hydrogels. These studies shed light on the role of mechanical factors in the regulation of EMT and may suggest approaches to target EMT during disease progression.