Abstract

The knowledge of cell mechanics is required to understand cellular processes and functions, such as the movement of cells, and the development of tissue engineering in cancer therapy. Cell mechanical properties depend on a variety of factors, such as cellular environments, and may also rely on external factors, such as the ambient temperature. The impact of temperature on cell mechanics is not clearly understood. To explore the effect of temperature on cell mechanics, we employed magnetic tweezers to apply a force of 1 nN to 4.5 µm superparamagnetic beads. The beads were coated with fibronectin and coupled to human epithelial breast cancer cells, in particular MCF-7 and MDA-MB-231 cells. Cells were measured in a temperature range between 25 and 45 °C. The creep response of both cell types followed a weak power law. At all temperatures, the MDA-MB-231 cells were pronouncedly softer compared to the MCF-7 cells, whereas their fluidity was increased. However, with increasing temperature, the cells became significantly softer and more fluid. Since mechanical properties are manifested in the cell’s cytoskeletal structure and the paramagnetic beads are coupled through cell surface receptors linked to cytoskeletal structures, such as actin and myosin filaments as well as microtubules, the cells were probed with pharmacological drugs impacting the actin filament polymerization, such as Latrunculin A, the myosin filaments, such as Blebbistatin, and the microtubules, such as Demecolcine, during the magnetic tweezer measurements in the specific temperature range. Irrespective of pharmacological interventions, the creep response of cells followed a weak power law at all temperatures. Inhibition of the actin polymerization resulted in increased softness in both cell types and decreased fluidity exclusively in MDA-MB-231 cells. Blebbistatin had an effect on the compliance of MDA-MB-231 cells at lower temperatures, which was minor on the compliance MCF-7 cells. Microtubule inhibition affected the fluidity of MCF-7 cells but did not have a significant effect on the compliance of MCF-7 and MDA-MB-231 cells. In summary, with increasing temperature, the cells became significant softer with specific differences between the investigated drugs and cell lines.

Highlights

  • The goal of our study was to analyze the effect of temperature on two distinct human epithelial breast cancer cells of different migratory capacity in 3D environments, such as MCF-7 and MDA-MB-231 cells at a temperature range covering at its higher end the temperature employed during hyperthermia treatments

  • Both cancer cell lines differ in their cytoskeletal structure, which is manifested in their distinct mechanical properties and invasive b­ ehaviors[30,31,39]

  • To investigate the effect of temperature on cell mechanics of breast cancer cells, we analyzed for each temperature (25 °C to 45 °C), the mechanical properties of well-known human breast carcinoma cells MDA-MB-231 and MCF-7 cells

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Summary

Introduction

Studies on the mechanical properties of cells have established a linkage between the specific physical properties of cancerous and healthy cells and differences in their respective s­ tructures[30,31]. The goal of our study was to analyze the effect of temperature on two distinct human epithelial breast cancer cells of different migratory capacity in 3D environments, such as MCF-7 and MDA-MB-231 cells at a temperature range covering at its higher end the temperature employed during hyperthermia treatments. We aim to link specific cytoskeletal components, such as the actin and myosin filaments as well as microtubules to the observed temperature-dependent (or induced) effects on these cells by comparing their overall respective thermorheological response

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