High-Speed Broadband Real-Time Monitoring of Cell Viscoelasticity Reveals Oscillatory Myosin Activity

Abstract

This article presents the investigation of the dynamic behavior of the cytoskeleton of live human cells, enabled by a recently-developed control-based approach on scanning probe microscope (SPM). Mechanical behaviors of live cells play an important role in various cell physiological and pathological activities, and have been studied via various techniques and approaches. Studies of evolutions of mechanical properties of live cell, however, are still rather limited and scarce, due to the limitations of current instruments including SPM for single cellular measurements. Particularly, currently nanomechanical measurements using SPM is too slow to excite the mechanical behavior and then measure the corresponding response of life biological species over a large frequency range (broadband). Moreover, large uncertainty is induced in the in-liquid nanomechanical measurement using SPM, as in the indentation quantification, the effects of the acceleration force from the cantilever motion and the hydrodynamic force are not accounted for. The main contribution of this article is the use of a control-based nanomechanical protocol to interrogate the viscoelasticity oscillation of live human prostate cancer cell (PC-3 cells) and its dependence on myosin activities. The experiment results show that as the oscillation of static elastic modulus reported earlier in the literature, the oscillation of dynamic viscoelastic modulus measured is also periodic with a 200-second period. Moreover, as the elastic modulus oscillation, both the amplitude and the period of the viscoelasticity oscillation also strongly depend on the myosin activities, and closely regulated by the calcium density of the cytoskeleton.