Xavier Trepat

Institut de Bioenginyeria de Catalunya

The human intestine is made up of more than 40 square meters of tissue, with a multitude of folds on its internal surface that resemble valleys and mountain peaks in order to increase the absorption of nutrients. The intestine also has the unique characteristic of being in a continuous state of self- renewal. This means that approximately every 5 days all the cells of its inner walls are renewed to guarantee correct intestinal function. Until now, scientists knew that this renewal could take place thanks to stem cells, which are protected in the so-called intestinal crypts, and which give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells towards the intestinal peaks was unknown.

In this study we deciphered the mechanisms leading the crypts to adopt and maintain their concave shape, and how the migration movement of the cells towards the peaks occurs, without the intestine losing its characteristic folded shape. The study combined computer modelling, led by Marino Arroyo, professor at the UPC, with experiments with intestinal organoids from mouse cells, and shows that this process is possible thanks to the mechanical forces exerted by the cells.

Using mouse stem cells and bioengineering and mechanobiology techniques, we developed mini- intestines, organoids that resemble the three-dimensional structure of peaks and valleys, recapitulating tissue functions in vivo. Using microscopy technologies developed by our group we carried out high-resolution experiments for the first time that allowed us to obtain 3D maps showing the forces exerted by each cell.

In addition, with this in vitro model, we showed that the movement of new cells to the peak is also controlled by mechanical forces exerted by the cells themselves, specifically by the cytoskeleton, a network of filaments that determines and maintains cell shape.

  • Reference
    Pérez-González C, Ceada G, Greco F, Matejčić M, Gómez- González M, Castro N, Menendez A, Kale S, Krndija D, Clark AG, Gannavarapu VR, Álvarez-Varela A, Roca-Cusachs P, Batlle E, Vignjevic DM, Arroyo M & Trepat X 2021 ‘Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration’. Nature Cell Biology, 23(7):745- 757.