Monitoring cell adhesion and characterizing cell viscoelasticity by using thickness shear mode (TSM) resonate sensor

Cell adhesion and mechanical properties are critical to physiological and pathological processes. Regulation of cell adhesion states is involved in tissue remodeling during morphogenesis and wound healing, cellular metaplasia, cell proliferation and tumor cell metastasis. Cell mechanical properties play an essential role in cell deformation under mechanical forces and other cell functions such as locomotion and cytokinesis. Because of the dominance of the cytoskeleton in cell structure and properties, measurement of the cell viscoelastic properties provides an effective approach to look into cytoskeleton, which plays an important role in cell growth, gene expression, protein synthesis, differentiation, migration and apoptosis. In this study, a functional biosensor system, which consists of acoustic wave biosensor array, cell culture, a mini-incubator, an impedance analyzer and a computer, was established to monitor cell adhesion and viscoelastic properties under controlled biological conditions. A multilayer acoustic wave sensor model that includes the thickness shear mode quartz resonator substrate, a cell-substrate interfacial layer and a cell layer in cell culture medium was constructed based on the state of cell adhesion to the substrate, which can be applied to predict the relationship between the resonant frequency and resistance change of the biosensor and physical properties of the interfacial layer and the cell layer. Experimentally, the dynamic processes of cell adhesion as function of cell seeding densities have been investigated. Using the theoretical model, the viscoelastic properties of cell layer are extracted by fitting the theoretical values of the resonator admittance near resonance with the measured spectrum. The results agree very well with the data obtained by other techniques.