Tissue Scale

Reconstituting Tissue Morphogenesis

Epithelium folding

At the multi-cellular scale, our interest is focused towards how cell monolayers – epithelia – deform during development. We have developed innovative assays to reconstitute tissue morphogenesis in vitro. We grew epithelia in alginate tubes to constrain them in a cylindrical geometry, and showed that their final tubular shape critical depends on the initial curvature of the tube, and the contractility of the cells (Maechler et al. J Cell Sci 2019). Optimizing an encapsulation technology for adhesive cells in hollow spheres of alginate (Alessandri et al. LOC 2016), and we showed that epithelium growing under the spherical confinement of those capsules fold by buckling (Trushko et al. Dev Cell 2020). This process is similar to the one we proposed for ESCRT-III, showing that biological surfaces are deformed through similar mechanisms at different scales. We also showed that the pressure arising within the capsule while the epithelium grows stops cell cycle above a threshold pressure (Di Meglio et al. Cell Rep 2022). We also studied how epithelial cells react to folding by creating pre-strained PDMS substrates that spontaneously roll upon cutting (Tomba et al. Dev Cell 2022). Using these substrates, we could show that upon rolling epithelial cells transiently increase their volume by 50%. This is because of a curvature-dependent change in the mechano-osmotic balance of the cell.

Nematic order of cells and morphogenesis

Because of their elongated shapes, cells in tissues can organize as nematic particles. Because of this multi-cellular order, forces exerted by each cell combine into stress-field dictated by the nematic field. We showed that by forcing the formation of integer topological defects (spirals, asters) in the nematic order of micropatterned monolayers of myoblasts, we can create compressive stress fields that cause the formation of multicellular protrusions (Guillamat et al. Nat Mat 2022). These protrusions are multi-cellular swirls, looking alike tornadoes, which structure is dictated by the integer nematic defect and the collective dynamics of cells around them.