BME7900 Seminar Series - Xavier Trepat, PhD
This week we welcome Dr. Xavier Trepat from the Institute for Bioengineering of Catalonia (ICREA), Barcelona, Spain. Mechanobiology of Intestinal Organoids Abstract: Intestinal organoids capture essential features of the intestinal epithelium such as folding of the crypt, spatial compartmentalization of different cell types, and cellular movements from crypt to villus-like domains. Each of these processes and their coordination in time and space requires patterned physical forces that are currently unknown. In this study, we map the three-dimensional cell-ECM and cell-cell forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the ECM and folds through apical constriction, whereas the transit amplifying zone pulls the ECM and elongates through basal constriction. Tension measurements establish that the transit amplifying zone isolates mechanically the stem cell compartment and the villus-like domain. A 3D vertex model shows that the shape and force distribution of the crypt can be largely explained by cell surface tensions following the measured apical and basal actomyosin density. Finally, we show that cells are pulled out of the crypt along a gradient of increasing tension, rather than pushed by a compressive stress downstream of mitotic pressure as previously assumed. Our study unveils how patterned forces enable folding and collective migration in the intestinal crypt. Bio: Xavier Trepat was trained in Physics and Engineering at the University of Barcelona. In 2004 he obtained his PhD from the Medical School at the University of Barcelona. He then joined the Program in Molecular and Integrative Physiological Sciences at Harvard University as a postdoctoral researcher. In January 2011 he became an ICREA Research Professor at the Institute for Bioengineering of Catalonia (IBEC). Trepat’s research aims to understand how cells and tissues grow, move, invade and regenerate in a variety of processes in health and disease. To achieve this, he has developed technologies to measure cellular properties at the micro- and nanoscales. He has then applied these technologies to identify fundamental mechanisms in cell biology and biophysics.