Fig. 5.

The alteration of dynamic polarity patterns in metastatic cells vs. noninvasive melanoma cells is explained by the proposed feedback mechanism. (A) SBcl2 cells display lower Rac1–PI3K activity and higher RhoA–ROCK activity than 1205Lu cells, as measured by immunoblotting of phosphorylated Akt and Akt (Rac1–PI3K) and phosphorylated MLC and MLC (RhoA–ROCK). (B) Assuming a decrease in ECM–Rac1 activation rate and increase in ECM–RhoA–ROCK activation rate in SBcl2 cells shifts the boundary between oscillatory and persistent regime and boundaries between random and oscillatory regimes toward the right, predicting smaller fraction of cells in the persistent Rac1–PI3K regime and a larger fraction in the random regime. (C) Comparison of model (in silico) and experiment (in vitro) results for the dependence of PI3K dynamics of SBcl2 cells on nanofabricated substrata coated with 10 μg/mL FN. (D) Axial ratio (the degree of aligned elongation) in the two cell lines. (E) D_y/T_y for 3 h of the two cell lines. The noninvasive SBcl2 cells have inhibited elongation and directional cell migration. *P < 0.05 for D_y/T_y values in each group using all paired Student’s t test.