Simultaneous time-varying viscosity, elasticity, and mass measurements of single adherent cancer cells across cell cycle

Abstract

Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. Evaluation of mass and viscoelasticity versus cell cycle can provide further insights into cell cycle progression and the uncontrolled proliferation of cancer. Using our pedestal microelectromechanical systems resonant sensors, we have developed a non-contact interferometric measurement technique that simultaneously tracks the dynamic changes in the viscoelastic moduli and mass of adherent colon (HT-29) and breast cancer (MCF-7) cells from the interphase through mitosis and then to the cytokinesis stages of their growth cycle. We show that by combining three optomechanical parameters in an optical path length equation and a two-degree-of-freedom model, we can simultaneously extract the viscoelasticity and mass as a function of the nano-scaled membrane fluctuation of each adherent cell. Our measurements are able to discern between soft and stiff cells across the cell cycle and demonstrated sharp viscoelastic changes due to cortical stiffening around mitosis. Cell rounding before division can be detected by measurement of mechanical coupling between the cells and the sensors. Our measurement device and method can provide for new insights into the mechanics of single adherent cells versus time.

Population distributions of single-cell adhesion parameters during the cell cycle from high-throughput robotic fluidic force microscopy

“…From the biological perspective, it means that cells in the M phase have smaller deformation capabilities, and therefore, they are stiffer. This result is in line with previous works 47 – 49 , however, the statistical difference with the other phases was not shown before using SCFS techniques. Our results highlight the differences in single-cell adhesion parameters in the M phase at the population level and suggest that it would be advantageous to investigate and selectively target M phase controlled protein expression to understand their role in cancer propagation better 50 , 51 .…”

Simultaneous Measurement of Single-Cell Mechanics and Cell-to-Materials Adhesion Using Fluidic Force Microscopy

“…60 The results were also consistent with Young's moduli (∼0.4 kPa) of MCF-7 cells cultured on Petri dishes for 1 day measured by optical tweezers, 65 and with others utilizing oscillation-induced deformation tests, where results between 0.2 and 0.3 kPa were obtained for MCF-7 cells with different morphologies. 66 The time constant τ 1 and τ 2 are important parameters to characterize the viscosity properties of cells (influenced mainly by the cytoplasm and actin networks 67,68 ), which reflect the time that cells need to relax after a deformation. The difference between τ 1 for less-spread and well-spread cells was statistically significant (p = 0.00044), whereas there was no significant difference in τ 2 between less-spread and well-spread cells (p = 0.29).…”

Combined High‐Speed Atomic Force and Optical Microscopy Shows That Viscoelastic Properties of Melanoma Cancer Cells Change during the Cell Cycle

“…This finding is even more apparent when viewing the cells’ mean values (Figure 5e, inset). The interpretation of this behavior is still unclear, but as cell stiffness and fluidity are also correlated with traction forces, [ 44 ] this behavior may be explained by increased actomyosin contraction and pressure generation, [ 45 ] increased traction forces, [ 46 ] or stiffening of the actin cortex [ 47 ] during cell cycles and division.…”