(112b) Role of Matrix Stiffness in Regulating the Response of Human Cancer Cells to Cytotoxic Compounds

Recent literature has emphasized the effects of biophysical properties of biomaterials-based cell culture microenvironments on multiple cell fates including proliferation, migration, and stem cell differentiation. In our study, using both two- and three-dimensional (2D and 3D) culture conditions, we explored the role of microenvironmental biophysical cues on cancer cell response to cytotoxic compounds. To test cell response on 2D, we employed polyacrylamide gels coated with collagen and for the 3D studies, we encapsulated the cells in alginate/collagen composite hydrogels. We used two different stiffness conditions (1kPa and 100 kPa) and collagen-coated tissue culture plastic as the control. These experiments suggested a previously uncovered property of matrix stiffness - their ability to influence cell response to cytotoxic compounds. Interestingly, our preliminary data also indicate that microenvironmental stiffness and not dimensionality (i.e. 2D vs. 3D) played a bigger role on cell cytotoxic responses. Additionally, the stiffness-dependent cytotoxic responses were cell specific, and at least in the case of 3D, dependent on the activation of the mechanotransductive protein, RhoA GTPase. Although further testing is warranted, this study suggests biomaterial matrix stiffness as an important parameter in the design of more predictive in vitro cell-based platforms for drug development and toxicity screening.