Biology

Dr. Namrata Gundiah
Indian Institute of Science, Bangalore

An organized and crosslinked extracellular matrix in tissues primarily contributes to its microstructure and material properties; these are also essential in determining organismal form, function, and homeostasis. A higher extracellular matrix stiffness alters the cellular adhesion, cytoskeletal dynamics, and receptor signaling. TGF-β is a highly expressed cytokine which acts as a tumor suppressor in normal conditions but as a promoter in cancers to contribute to epithelial to mesenchymal transitions. The biochemical signaling pathways associated with TGF-β have been well characterized but its correlation with cell mechanics is under explored. We hypothesized that in breast cancers, exposure to active TGF-β leads to increased cellular deformability that facilitates transport through narrow spaces. We also hypothesized that TGF-β treatment promotes increased cellular traction forces. We indented breast cancer cells with differential invasiveness (MCF-7 and MDA-MB-231) using an atomic force microscope (AFM) to quantify the cellular stiffness using a modified Hertzian model with thickness correction. We also performed stress relaxation experiments to characterize the viscoelastic properties of the cells after TGF-β treatment. Our results show a temporal context dependent influence of TGF-β on the cell mechanical properties that correlated with the invasive potential of cells. Confocal imaging showed increased actin fiber expression due to TGF-β treatment that suggest differential microstructural organization of the cytoskleleton. Current investigations are aimed at linking cell traction forces on cells treated with TGF-β, quantified using a regularized Fourier Transform Traction Cytometry, on a range of substrate stiffness. Such studies provide valuable insights into the mechanobiology of cell- substrate interactions that are important in cancer metastasis.