Curling of Epithelial Monolayers Reveals Coupling Between Active Bending and Tissue Tension
J. Fouchard, T.P.J. Wyatt, A. Proag, A. Lisica, N. Khalilgharibi, P. Recho, M. Suzanne, A. Kabla, G. Charras
PNAS 117(17):9377–9383 (2020), doi:10.1073/pnas.1917838117
Abstract
Significance
Epithelial monolayers are sheet-like tissues composed of cells connected to one another that line the surface of all organs. These tissues change shape and bend during developmental morphogenesis or early in tumor formation. Yet, the amplitude of bending forces and how they integrate with tensile and compressive forces within the plane of the tissue remain largely unknown. By revealing the ability of epithelial monolayers to curl, we demonstrate that the polarization of contractile molecular motors within the tissue thickness generates high spontaneous curvature of the sheet. We quantify the corresponding torques and show that stretch and compression within the tissue plane can substantially impact curling. Such mechanical coupling could be at play during epithelial morphogenesis.
Summary
Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.