Cell motility probed by noise analysis of thickness shear mode resonators.

The quartz crystal microbalance (QCM) technique is an emerging bioanalytical tool to study the behavior of animal cells in vitro. Due to the high interfacial sensitivity of thickness shear mode (TSM) resonators it is possible to monitor the formation and breakage of cell-matrix interactions and changes in viscoelasticity of the cell bodies, as well as minute cell volume alterations by the time course of their resonance frequency even with millisecond time resolution. We found that mammalian MDCK-II cells grown on TSM resonators impose characteristic fluctuations on the resonance frequency, which are a quantitative indicator for dynamic activities of the cells on the surface and report on their vitality and motility. Applying noise analysis to the fluctuating resonance frequency allows one to quantify the response of the cells to environmental changes such as osmotic stress, addition of fixation reagents, or the influence of drugs such as cytochalasin D. The corresponding power density spectra of the noise imposed on the resonance frequency by the dynamic activities of the cells show a characteristic resonance at 1-2 Hz, which can be substantially altered by osmotic stress, fixation agents, or cytochalasin D. Comparison of QCM-based fluctuation readings with electric cell--substrate impedance sensing (ECIS)--a well-established technique to monitor cell dynamics-provides substantially different results, indicating that both techniques may complement each other with respect to their biological information. Whereas ECIS readings report solely on cell shape changes, QCM-based fluctuation analysis is also influenced by fluctuations in the viscoelasticity of the cell bodies.