Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model

Salmanzadeh A, Elvington ES, Roberts PC, Schmelz EM, Davalos RV. Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model. Integr Biology Quantitative Biosci Nano Macro. 2013;5: 843–852. doi:10.1039/c3ib00008g

Currently, conventional cancer treatment regimens often rely upon highly toxic chemotherapeutics or target oncogenes that are variably expressed within the heterogeneous cell population of tumors. These challenges highlight the need for novel treatment strategies that (1) are non-toxic yet able to at least partially reverse the aggressive phenotype of the disease to a benign or very slow-growing state, and (2) act on the cells independently of variably expressed biomarkers. Using a label-independent rapid microfluidic cell manipulation strategy known as contactless dielectrophoresis (cDEP), we investigated the effect of non-toxic concentrations of two bioactive sphingolipid metabolites, sphingosine (So), with potential anti-tumor properties, and sphingosine-1-phosphate (S1P), a tumor-promoting metabolite, on the intrinsic electrical properties of early and late stages of mouse ovarian surface epithelial (MOSE) cancer cells. Previously, we demonstrated that electrical properties change as cells progress from a benign early stage to late malignant stages. Here, we demonstrate an association between So treatment and a shift in the bioelectrical characteristics of late stage MOSE (MOSE- L) cells towards a profile similar to that of benign MOSE-E cells. Particularly, the specific membrane capacitance of MOSE-L cells shifted toward that of MOSE-E cells, decreasing from 23.94 ± 2.75 to 16.46 ± 0.62 mF m(-2) after So treatment, associated with a decrease in membrane protrusions. In contrast, S1P did not reverse the electrical properties of MOSE-L cells. This work is the first to indicate that treatment with non-toxic doses of So correlates with changes in the electrical properties and surface roughness of cells. It also demonstrates the potential of cDEP to be used as a new, rapid technique for drug efficacy studies, and for eventually designing more personalized treatment regimens.

Finding crossover frequency of cells based on their movement towards top or bottom half of the channel. MOSE-L cell movement in the sample channel (a) without applying any electric field, (b) due to applying 200 VRMS and negative DEP force at 5 kHz and (c) 200 VRMS and positive DEP force at 30 kHz. Normalized cell distributions corresponding to (d) no DEP force in the control (a), (e) negative DEP in (b), and (f) positive DEP in (c).