Cell mechanical properties of human breast carcinoma cells depend on temperature

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.

Viscoelasticity, Like Forces, Plays a Role in Mechanotransduction

“…The majority of approaches to query the viscoelastic behavior of cells utilize forced induced deformations or probes ( Wirtz, 2009 ) on relatively short time scales due to experimental requirement and feasibility. Efforts to gauge the elastic aspect of cell viscoelasticity involve atomic force microscopy (AFM) ( Haase and Pelling, 2015 ; Fischer et al, 2017 , Mierke et al, 2017 , Fischer et al, 2020 ), hydrodynamic stretching ( Gossett et al, 2012 ), optical cell stretcher ( Kunschmann et al, 2017 , Kunschmann et al, 2019 ; Mierke et al, 2020 ), optical laser tweezers ( Lincoln et al, 2004 ), magnetic tweezers ( Amblard et al, 1996 ; Aermes et al, 2020 , Aermes et al, 2021 ), microrheology ( Mason and Weitz, 1995 ; Crocker and Hoffman, 2007 ), magnetic resonance elastography ( Muthupillai et al, 1995 ; Zhang et al, 2021 ), micropipette suction ( Hochmuth, 2000 ) and uniaxial stretching rheometry ( Desprat et al, 2005 ) ( Figure 1 ). The viscous part of the reaction of cells to mechanical probing has been determined employing biophysical techniques encompassing microrheology ( Mason and Weitz, 1995 ; Crocker and Hoffman, 2007 ), micropipette suction ( Hochmuth, 2000 ), fluorescent rotor protein ( Kuimova et al, 2008 ), AFM ( Rebelo et al, 2013 ), electronic spin resonance ( Mastro and Keith, 1984 ) and optical laser tweezers ( Ługowski et al, 2002 ) ( Table 1 ).…”

Nanomechanical and microrheological properties of bladder cancer cells at cellular and spheroid levels

“…Cells are not fulfilling this assumption because they reveal viscoelastic nature 31,56 . Moreover, cell softening indicated by negative values of the rigidity index can be, supposedly, related to the larger fluidity of cancer cells 57,58 . Thus, in our next steps, we quantify the microrheological properties of the studied bladder cancer cells.…”

The Pertinent Role of Cell and Matrix Mechanics in Cell Adhesion and Migration

“…Microrheological approaches, such as Magnetic tweezers (Kollmannsberger and Fabry, 2007 ; Sarkar and Rybenkov, 2016 ), Magnetic twisting cytometry, and Single article tracking approaches are both still state-of-the-art biophysical techniques that can be refined by including temperature issues (Aermes et al, 2021 ), cytoskeletal coupling or membrane receptor strengths to characterize the mechanophenotype of cells.…”