Fig. 3: Programmable RGD/integrin and HAVDI/N-cadherin ligations regulate YAP signaling.

a Left: Representative YAP images for state switching from “OFF” for initial 1 d to “ON” for subsequent 1 d. Right: Quantification of YAP nuc/cyto ratios (from left to right n = 67, 74, 93, 82 cells). Cells were cultured on continuously “OFF” and “ON” substrates for 2 d as control groups. b Left: Representative YAP images for state switching from “ON” for initial 1 d to “OFF” for subsequent 1 d. Right: Quantification of YAP nuc/cyto ratios (from left to right n = 82, 85, 71, 67 cells). Cells were cultured on continuously “ON” and “OFF” substrates for 2 d as control groups. c Left: Representative YAP images for state switching from “ON” for initial 1 d to “Dual ON” for subsequent 1 d. Right: Quantification of YAP nuc/cyto ratios (from left to right n = 82, 85, 96, 67 cells). Cells were cultured on continuously “ON” and “Dual ON” substrates for 2 d as control groups. d Left: Representative YAP images for state switching from “Dual ON” for initial 1 d to “ON” for subsequent 1 d. Right: Quantification of YAP nuc/cyto ratios (from left to right n = 67, 81, 79, 82 cells). Cells were cultured on continuously “Dual ON” and “ON” substrates for 2 d as control groups. e Schematic of the evolution of the mechanical microenvironment during mesenchymal development. f Schematic for achieving simultaneously increasing RGD and decreasing HAVDI on the substrates to mimic the mechanical microenvironment in e. g Concentrations of RGD and HAVDI were simultaneously varied every 6 h for the same conditions as f, until a total culture time of 24 h. h Left: Representative YAP images for the same conditions as g. Right: Quantification of YAP nuc/cyto ratios (from left to right n = 71, 79, 97, 94 cells). Data are presented as mean ± s.e.m., and p values were obtained using one-way ANOVA followed by Tukey’s post hoc test (a–d, h). Scale bars: 30 µm (a–d, h). Source data are provided as a Source Data file.