Investigating longitudinal changes in the mechanical properties of MCF-7 cells exposed to paclitaxol using particle tracking microrheology

Abstract

Evidence suggests that compression and shear wave elastography are sensitive to the mechanical property changes occuring in dying cells following chemotherapy, and can hence be used to monitor cancer treatment response. A qualitative and quantitative understanding of the mechanical changes at the cellular level would allow to better infer how these changes affect macroscopic tissue mechanical properties and therefore allow the optimization of elastographic techniques (such as shear wave elastography) for the monitoring of cancer therapy. We used intracellular particle tracking microrheology (PTM) to investigate the mechanical property changes of cells exposed to paclitaxol, a mitotic inhibitor used in cancer chemotherapy. The average elastic and viscous moduli of the cytoplasm of treated MCF-7 breast cancer cells were calculated for frequency ranges between 0.2 and 100 rad s(-1) (corresponding to 0.03 and 15.92 Hz, respectively). A significant increase in the complex shear modulus of the cell cytoplasm was detected at 12 h post treatment. At 24 h after drug exposure, the elastic and viscous moduli increased by a total of 191.3 Pa (>8000×) and 9 Pa (∼9×), respectively for low frequency shear modulus measurements (at 1 rad s(-1)). At higher frequencies (10 rad s(-1)), the elastic and viscous moduli increased by 188.5 Pa (∼60×) and 1.7 Pa (∼1.1×), respectively. Our work demonstrates that PTM can be used to measure changes in the mechanical properties of treated cells and that cell elasticity significantly increases by 24 h after chemotherapy exposure.