Fig. 4: E-cad KO cells are eliminated through increased stress fluctuations.

a, Isotropic stress susceptibility versus distance from the interface, normalized to the highest value. n = 18 videos from N = 5 independent experiments including mixed cultures and collisions. b, Snapshots of actin dynamics at the interface. Maximum projections and side view of MDCK E-cad KO LifeAct-GFP (green) and MDCK WT LifeAct-Ruby (white). Right: zoomed-in images on the maximum projection of E-cad KO cells protruding below WT cells. The apical interface is indicated by the magenta line drawn based on the WT LifeAct-Ruby signal (not shown). c, Phase-contrast and fluorescence images of the boundary (red arrows) before (left) and 2 h after 20 µm blebbistatin (Blebb.) addition (right). d, Isotropic stress susceptibility versus distance from the interface for each cell type, before (dots) and after (rectangles) the addition of blebbistatin normalized to the highest value. n = 10 videos from N = 2 independent experiments. e, Left: ensemble average stress heat map before E-cad KO extrusions. Extrusions considered within a 30-µm band from the interface. Stresses were averaged up to 40 min before the automated detection of extrusion, excluding the time point of completed extrusion. Stress fields were oriented (top, KO; bottom, WT) based on the E-cad KO fluorescence signal (Methods). Right: average stress heat map of random positions in E-cad-KO-occupied area at the interface. n = 798 extrusions (E-cad KO), n = 750 KO random positions from four independent experiments. f, Average stress heat map before WT bulk extrusions. n = 741 extrusions from N = 4 independent experiments. g, PDFs of the average isotropic stress distribution before extrusion detection (WT cell bulk elimination, blue; KO cell interface elimination, green; and random KO interface position, black) corresponding to e and f. h, Temporal evolution of the mean isotropic stress susceptibility before (t < 0) and briefly after an extrusion event. t = 0 indicates the time point of automated extrusion detection. Random position of E-cad KO cells at the interface, black; E-cad KO elimination, green; WT cell elimination, blue. Susceptibility is averaged within a square of size 60 µm around one extrusion event. Normalized to the initial value, n = 726 extrusions (E-cad KO), n = 1,050 KO random positions and n = 334 extrusions (WT) in n = 6 videos from N = 2 independent experiments. Data are presented as mean values ± s.d. Scale bars, 50 µm (c); 10 µm (b).

Source data