Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics

We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions.

Figure 1

Experimental setup. A voltage signal, controlled by labview software, is applied to the counter electrode of the cell-substrate impedance sensor and the current measured at the working electrode by a current-to-voltage converter. The impedance is given by $Z=V_{\text{in}}/I_{\mathrm{out}}$.

Figure 2

Time evolution of impedance $\left|Z\right|$ (upper line), modeled ohmic resistance ${\mathrm{R}}_{\mathrm{ohm}}$(F) (middle line) and normalized projected area F (bottom line) for (a) AX2-WT and (b) tal${\mathrm{A}}^{-}$ cells. Time evolution of the projected area for (c) a selected AX2 cell and (d) a tal${\mathrm{A}}^{-}$ cell, shown together with the corresponding cell shapes. (e) Averaged projected cell area and contact area obtained from bright-field (BF) and reflection interference contrast microscopy (RICM) for WT and tal${\mathrm{A}}^{-}$ cells and the corresponding ratios (relative contract). (f, g) Time evolution of the contact area (RICM) for a WT and a tal${\mathrm{A}}^{-}$ cell. (h) Examples of BF and RICM images of WT and tal${\mathrm{A}}^{-}$ cells. Contact area (RICM, red lines) and contour area (BF, blue lines).

Figure 3

(a) Selected impedance time series for every cell line. (b) Wavelet scalograms for GFP-$\alpha$-tubulin and tal${\mathrm{A}}^{-}$ impedance time series. Low-pass filtered signals (dashed lines). On the right-hand side time-averaged scalograms and power spectra (PSD) are shown. (c) Standard deviations of high-pass filtered impedance signals. (d) Motility cycle periods. (e) Maximal adhesion force measured with AFM-SCFS. (f) Shear stress detachment assay. At indicated time points detached cells were counted.

Figure 4

Selected time series of the projected area, wavelet scalogram, time-averaged scalogram, and power spectrum for an AX2 cell and a tal${\mathrm{A}}^{-}$ cell.

Figure 5

Motility cycle periods calculated from projected cell area time series.