FIG. 5.

Physiological effects of cyclic mechanical forces in gut-on-a-chip devices. (a) Caco-2 cells under flow and cyclic mechanical stimuli form a well-defined polarized 3D topography, (top left) SEM image of villi, (top right) Z-stacked fluorescence image of villi (nuclei: blue, F-actin: green, and mucin 2: magenta), and (bottom row) images of a villus's top (T) and middle (V) cross sections (ZO-1 protein: red, F-actin: green). Adapted with permission from Kim et al., Integr. Biol. 5(9), 1130 (2013). Copyright 2013 Oxford University Press.⁹² (b) Organoid-derived epithelial cells form a villi-crypt topography in the presence of fluid flow and peristalsis (F-actin: magenta, Muc5AC: green, and nuclei: blue). Adapted with permission from Kasendra et al., Sci. Rep. 8(1), 2871 (2018). Copyright 2018 authors, licensed under a Creative Commons Attribution (CC BY) license.⁷¹ (c) The effect of pulsation on bacterial growth. The images (top-view of the epithelium) show the interaction of the E. coli bacteria (green) and villi topography (gray scale). The bacterial fluorescence intensity is much higher upon the loss of the mechanical strain (-Str), indicating significant overgrowth. Adapted with permission from Kim et al., Proc. Natl. Acad. Sci. 113(1), E7 (2016).⁹⁴