Fig. 3: TRPC3/6-mediated mechanosensing triggers calcium transient at the epithelial fold under EGFR activation.
From: An actin bracket-induced elastoplastic transition determines epithelial folding irreversibility
a Bending plastic ratio, ψ, for τ = 30 min under drug treatment conditions targeting intracellular calcium chelation, and mechanosensitive channel inhibition. The conditions included treatments with BAPTA-AM (p = 2.11e − 7), GsMTx4 (p = 5.28e − 7), Pico145 (p = 0.00856), Pyr3 (p = 2.70e − 8), and SAR7334 (p = 5.15e − 9). b Time-lapse images of GCaMP6s 10 min after indentation initiation. Calcium transients occurred in the apical region (arrows). Five experiments were repeated independently. c Time variations of calcium concentrations around the apex 10 min after indentation initiation. d, e Spatial distributions of calcium transient frequency: before, 10 min, and 20 min after indentation initiation. Map view (d) and distribution along the epithelium contour averaged across samples (e). Dotted lines indicate epithelium contours. Data represent the mean ± s.e. (N = 5). f Calcium transient frequency at apical and basal regions (N = 5 biological replicates, p = 0.0101). g Calcium transient frequency around the apex under drug treatment conditions targeting intracellular calcium chelation, mechanosensitive channel inhibition, and EGFR inhibition, as well as under a condition of low-curvature folding. The conditions included BAPTA-AM (p = 0.00277), GsMTx4 (p = 0.0574), PD153035 (p = 0.00601), and low-curvature folding (p = 0.00445). h ERK-FRET ratios of individual cells for indentation only (p = 1.56e − 9) and in the presence of mechanosensitive channel inhibitor, GsMTx4 (p = 0.00568) at t = 0 and the time of peak ratio. Box plots in (a) and (e–h): center, median; bounds, 25th and 75th percentiles; whiskers, min, and max; *P < 0.05, **P < 0.01, ***P < 0.001 (two-sided Welch’s t-test). N indicates a biologically independent sample. EGFR epidermal growth factor receptor, ERK extracellular signal-related kinase, FRET Förster resonance energy transfer, TRPC transient receptor potential canonical. Source data are provided as a Source Data file.
