(A) Phospho-p38γ levels are elevated in the MDA-MB-231 BC cell line compared to non-tumorigenic MCF-10A mammary epithelial cells. (B) shRNA knockdown of p38γ in MDA-MB-231 cells. (C) (left) Cell shapes of scrambled and shp38γ cells. (right) Quantification of cell shape difference by aspect ratio measurement (length/width) (*p = 7.82 × 10−7, n = 22 cells for scrambled, n = 27 cells for shp38γ, scale bar = 25 μm). (D) Actin fiber orientation differs between scrambled and shp38γ cells. (**p<0.01, n = 16 for scrambled, n = 22 for shp38γ, scale bar = 20 μm). (E) (left) Representative images from time lapse movies (Movies 1–2) of scrambled and shp38γ cells, demonstrating the characteristic mesenchymal-like motility of scrambled cells (top) and the disjoint crawling motion of shp38γ cells (bottom) (scale bar = 10 μm). (right) shp38γ cells are significantly slower than scrambled cells (*p = 3.34 × 10−5, n = 30 cells per cell line). (F) Preliminary computational models of scrambled and shp38γ cells qualitatively represent the locomotion of each cell type (see text for details). Arrows point to out-of-phase lamellipodial oscillations. The actin fibers are in red and the nucleus is blue.