2023 AIChE Annual Meeting
Dynamic Modulation of Matric Stiffness Regulates Apoptosis in Breast Cancer Cells
Breast cancer is the second leading cause of cancer death in women , with it accounting for 1/8th of cancer cases diagnosed worldwide. An increase in the stiffness of the tissue in the surrounding area of breast tumors is characteristic of breast cancer progression. Apoptosis or programmed cell death is known to be blocked in cancer cells leading to enhancement in tumor progression. Previous studies have shown that increased extracellular matrix stiffness reduces apoptosis in cancer cells and is potentially a mechanism by which cancer cells evade chemotherapeutic drugs. Most literature reports involving monitoring the impact of tumor mechanics on cancer cells have been performed on substrates with static mechanical properties, however, substrates with dynamic control of the mechanics provide an approach for monitoring how temporal changes in matrix mechanical properties impact apoptosis and tumor progression. Here, dynamic hyaluronic acid-based hydrogels that mimic the stiffness of normal and tumorigenic breast microenvironments were synthesized and characterized. MDA-MB-231 breast cancer cells were then cultured on the substrates and immunofluorescence staining was conducted to monitor the levels of cleaved caspase-3, an apoptosis marker. Quantification of cleaved caspase-3 staining revealed that when the modulus was replicative of a tumorigenic breast environment, the percentage cleaved caspase-3 positive cancer cells was reduced in comparison to when cells were cultured on hydrogels mimicking the mechanical properties of normal breast tissue. Furthermore, the percentage of cells staining positive for cleaved caspase-3 dynamically increased when the modulus of the hydrogels gradually softened over time. These findings indicate a role for matrix mechanics in regulating apoptosis in cancer cells. Overall, this hydrogel system provides a platform for examination of how dynamic modulation of matrix mechanics impacts cell phenotype.