Cell-substratum interactions as a predictor of cytotoxicity

An in vitro toxicity assay based on an emerging biosensor technology referred to as ECIS (electric cell-substrate impedance sensing) has been developed and tested. In ECIS, adherent cells are cultured, on small gold electrodes and electrical impedance is monitored with a computer-interfaced instrument. Subtle changes in cell morphology and behavior including cell motility can be detected with this approach. Confluent cell monolayers (WI-38/VA13 fibroblastic and MDCK epithelial cells) were exposed to varying concentrations of four detergents (Tween 20, benzalkonium chloride, Triton X100, and sodium lauryl sulfate). ECIS measurements were used to follow subsequent changes of the overall impedance of the cell monolayer and of cell motions detected as impedance fluctuations. Analysis of these measurements can correctly rank the detergents according to their established in vivo toxicity. Of particular interest was the dramatic increase of impedance fluctuations sometimes recorded from cells upon exposure to the toxicants. This occurred at times and detergent concentrations below those showing a decline in overall impedance; the effect was particularly evident in the MDCK cells.