Fig. 3: Morphological bistability with mechanosensitivity of crypts.
From: Mechanochemical bistability of intestinal organoids enables robust morphogenesis
a, Schematic of the feedback mechanism that involves both mechanical forces and mechanosensitivity of crypt cells: lumen volume and apical-to-basal tension difference affect the curvature of the crypt due to passive force balance, whereas active mechanosensing can result in the geometry/mechanics of the crypt feedback on apical/basal tensions. b, Theoretical prediction of the dependence of crypt differential tension on lumen volume, in both bulged and budded organoids, when assuming mechanosensation: in bulged organoids, inflation results in crypt opening that negatively regulates tensions by mechanosensing, whereas budded organoids have structurally stable crypts that do not open on inflation that, thus, do not trigger an active response. c,d, Left, Myh9-GFP distribution on crypt surfaces, before and after lumen inflation (with time interval between these two states being 15–30 min). After lumen inflation, bulged crypts show basal actomyosin relocation (yellow arrow). Right, apical-to-basal Myh9-GFP intensity ratio in bulged (c; N = 7) and budded (d; N = 19) crypt cells. Both raw data and mean values ± s.d. of data are shown. e, Experimental data (symbols, presented as mean values ± s.d.) and fitting (line) of mechanosensitivity, both apical-to-basal Myh9-GFP intensity ratio and crypt radius after lumen inflation are normalized by their values before inflation. Both bulged (N = 24) and budded (N = 28) samples are included. The fitting curve is y = x–b. f, Influence of sensitivity factor n on the predicted threshold for organoids to remain in the budded/bistable state on lumen inflation, and comparison with experimental data of bulged (N = 11) and budded (N = 28) samples for the estimated value of n = 1.0 (inferred from the best-fit value in e; see the main text and Supplementary Note 4 for details). Scale bars, 50 µm (organoid); 20 µm (zoomed-in image).
