Optomechanical microrheology of single adherent cancer cells

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.