Symposium Series Physics and Medicine (8)
Pressure, density, elasticity are classical physical properties, which are required to fully describe the processes in human cell assemblies – for example, to distinguish tumours from healthy tissue or to stimulate the regrowth of nerve cells. These examples illustrate how physics can provide new stimuli for basic medical research.
Today, modern physical methods and physical thinking are being transferred towards physiological application worldwide. In order to promote the exchange between different researchers and working groups, the Max Planck Zentrum für Physik und Medizin is starting a new series of public mini-symposia, in which two to three scientists from North America, Europe or Asia will present their work virtually.
To take part in the symposia, please register for MPL's scientific lectures newsletter (please ensure that you tick the "scientific lecture" checkbox). We will send the Zoom links about one hour before the symposium starts.
The schedule for Tuesday, April 27th in detail:
15:00 - 15:05 Welcome
15:05 - 15:50 Guillaume Charras, UCL: Cortical tension: from signalling to tissue shape
— 10 min break —
16:00 - 16:45 Xavier Trepat, IBEC Barcelona: Mechanobiology of intestinal organoids
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.
— 10 min break —
16:55 - 17:40 Margaret Gardel, University of Chicago: Stresses and Ratchets in Epithelial Morphogenesis
Cell shape changes in epithelial remodeling is driven by changes in the of cell-cell junction length. Junction shortening has been described as a morphogenetic ratchet whereby periodic contractility, driven by pulsatile RhoA activity, produces transient contraction to result in irreversible junction shortening. In fact, pulsatile Rho activity is observed in diverse morphogenetic processes, indicating that the spatiotemporal structure of Rho GTPase signaling may be an important feature of cellular contractile machines. We have exploited optogentic control of RhoA, in conjunction with physical modeling, to reveal the adaptive mechanics and asymmetric nature of the morphogenetic ratchet. This pathway likely represents a homeostatic mechanism to regulate junction lengths, where small fluctuations in exogenous RhoA are buffered but longer patterned RhoA activity directs morphogenetic change. Other data in our lab suggests that the endogenous stress fluctuations arise from cell cycle dependencies. More broadly, the impact of this work demonstrates a versatile strategy to query the force-sensitive behavior of sub-cellular organelles in situ that underlie adaptive mechanics in tissue morphogenesis.
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