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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.
Highlights
Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease
Recent work has shown that both internal and external forces act through the cytoskeleton to influence the mechanical properties and behavior of cells as they progress through the growth cycle[13,14]
The laser is alternately passed through the cell and outside the cell to measure the variations in the optical path length (OPL)
Summary
Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. The rise of many techniques to study mechanical properties (e.g., viscoelasticity) of cells has led to an increase in understanding of mechanical properties and disease, and include methods such as atomic force microscopy (AFM)[2,16,17], micropipette aspiration[13,18,19], and magnetic twisting cytometry These techniques probe the behavior of cells at different length and time scales, and employ different stress–strain magnitudes and behaviors. The first investigation of a time-varying simultaneous estimation of viscoelasticity and mass for individual adherent cells over the cell cycle We achieve this by adding a temporal dimension to our recently developed micro-resonator based technique for measuring the biophysical properties of individual adherent cells. The ability of our technique to resolve viscoelastic properties and mass simultaneously can help to elucidate intricate dynamics of the cell cycle
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