Optomechanical microrheology of single adherent cancer cells

Abstract

There is a close relationship between the mechanical properties of cells and their physiological function. Non-invasive measurements of the physical properties of cells, especially of adherent cells, are challenging to perform. Through a non-contact optical interferometric technique, we measure and combine the phase, amplitude, and frequency of vibrating silicon pedestal micromechanical resonant sensors to quantify the “loss tangent” of individual adherent human colon cancer cells (HT-29). The loss tangent, a dimensionless ratio of viscoelastic energy loss and energy storage — a measure of the viscoelasticity of soft materials, obtained through an optical path length model, was found to be 1.88 0.08 for live cells and 4.32 0.13 for fixed cells, revealing significant changes (p < 0.001) in mechanical properties associated with estimated nanoscale cell membrane fluctuations of 3.86 0.2 nm for live cells and 2.87 0.1 nm for fixed cells. By combining these values with the corresponding two-degree-of-freedom Kelvin-Voigt model, we obtain the elastic stiffness and viscous loss associated with each individual cell rather than estimations from a population. The technique is unique as it decouples the heterogeneity of individual cells in our population and further refines the viscoelastic solution space.

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

“…To explicitly decouple the viscoelastic moduli of individual cells from a sample population, the membrane fluctuation (height oscillation) is combined with a mechanically-induced and optically-measured phase-shift of each cell using an optical path difference model. The LDV measures the time-derivative of the OPL and is used to determine the membrane oscillation of the cell 27 , 46 , 47 . Figure 1 C is a schematic overview of the optical path of the laser in conjunction with difference in refractive index of each surrounding layer (air, media, cell) of its travel length.…”

“…As in previous studies 1 , 24 – 27 , 47 , our sensor-cell configuration is modelled as a 2-DOF suspended mass model where the cell is represented by a Kelvin-Voigt viscoelastic solid with a mass ( m 2 ), elastic stiffness ( k 2 ), and viscous coefficient ( c 2 ) connected to the sensor. The sensor mass ( m 1 ) is also connected to the fixed substrate by a second Kelvin-Voigt spring-damper ( k 1 , c 1 ).…”