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.

Ultrasound Elastography: Review of Techniques and Clinical Applications

“…The adoption of elastography to new clinical applications, such as characterizing highly heterogeneous tumor masses or organs, will likely require the adoption of more complex modeling that accounts for tissue viscoelasticity 25, 26. This is in part due to a tumor's highly heterogeneous microenvironment, which contains stiff elastic regions (e.g., fibrosis, calcifications) as well as soft viscous regions (e.g., blood pools, cystic degeneration areas) with variations at different length-scales 27-29.…”

Particle tracking in drug and gene delivery research: State-of-the-art applications and methods

“…Later studies demonstrated the power of PTM for probing cellular microstructure, including the relatively increased stiffness of the interphase nucleus compared to the cytoplasm [101], the spatial uniformity of the viscoelasticity in the cytoplasm of developing Caenorhasbditis elegans embryos [102], the relationship between matrix stiffness and cellular stiffness [103], and the changes in mechanical properties of cancer cells in response to chemotherapy treatment [104]. In these cases, the drag exerted by the fluid on the NP reveals the local elasticity or viscosity.…”

Supersonic Shear Wave Elastography of Response to Anti-cancer Therapy in a Xenograft Tumor Model

“…Quantitative ultrasound has also been reported to be able to monitor tissue changes in response to cancer treatment administration (SadeghiNaini et al 2013). Stiffness, as evaluated with ultrasound, could also be an interesting parameter for assessment of treated tissues, because response to therapy is associated with cell death and changes in the biomechanical properties of the tumors (El Kaffas et al 2013). Ultrasound elastography is a relatively recent technique that reflects tissue stiffness.…”