Fig. 2. RPE1 cells exhibit intermittent migration following a stick-slip motion.

(A) Scheme of the force asymmetry analysis: The normalized quadrupole was extracted from the 1D projection of the stress profile of an adherent cell (color-coded stress map and 1D profile depending on the direction of applied traction forces $\overrightarrow{\mathit{F}}$ exerted: red in and cyan against the direction of migration). Dynamic measurements revealed a symmetric spatial force profile during static spreading and an asymmetric distribution during migration phases. Inset: average force asymmetry during static and mobile phases of several cells (n = 10). ****P < 0.0001 (unpaired, two-tailed t test). (B) Cell length and total force correlation: increase during spreading phase and decrease during migration. (C) Referenced kymograph of RPE1 cells stably expressing vinculin-eGFP showing a continuous attachment of the front, while adhesions in the rear detached and reattached during one migration cycle (scale bar, 10 μm). Tracking the front, rear, and nucleus position over time could further represent this destabilization of the rear. (D) Deduced scheme of the proposed stick-slip migration mechanism: During nonmotile spreading (stick), the cell builds up a high traction force that eventually will overcome adhesion strength in the perspective rear of the cell. Upon the retraction of the rear, the cell shortens and lowers its mechanical interaction with the substrate to initiate migration (slip). (E) Schematic of the model and parameters as defined in the text. (F) Phase diagram of dynamic behaviors predicted by the model, as a function of the actin turnover rate λ and phenomenological parameter α (arbitrary units). Dashed lines show different values of the maximal contractile force F_max = $\frac{\mathbf{\chi }\mathbf{\alpha }}{\mathbf{\lambda }}$. (G) Example of stick-slip dynamics predicted by the model. Dynamical eqs. S2 and S3 are solved numerically with vm = 0.5, v_p= 0.5, λ = 1, μ = 1, α = 1 (arbitrary units). Blue, orange, and brown line show rear, nucleus, and front position over time, respectively. Green line depicts the relative traction force level F.