Architecture and migration of an epithelium on a cylindrical wire

Abstract

In a wide range of epithelial tissues such as kidney tubules or breast acini, cells organize into bidimensional monolayers experiencing an out-of-plane curvature. Cancer cells can also migrate collectively from epithelial tumors by wrapping around vessels or muscle fibers. However, in vitro experiments dealing with epithelia are mostly performed on flat substrates, neglecting this out-ofplane component. In this paper, we study the development and migration of epithelial tissues on glass wires of well-defined radii varying from less than 1 μm up to 85 μm. To uncouple the effect of out-of-plane curvature from the lateral confinement experienced by the cells in these geometries, we compare our results to experiments performed on narrow adhesive tracks. Because of lateral confinement, the velocity of collective migration increases for radii smaller than typically 20 μm. The monolayer dynamics is then controlled by front-edge protrusions. Conversely, high curvature is identified as the inducer of frequent cell detachments at the front edge, a phenotype reminiscent of the Epithelial−Mesenchymal Transition. High curvature also induces a circumferential alignment of the actin cytoskeleton, stabilized by multiple focal adhesions. This organization of the cytoskeleton is reminiscent of in vivo situations such as the development of the trachea of the Drosophila embryo. Finally, submicron radii halt the monolayer, which then reconfigures into hollow cysts.collective cell behaviors | out-of-plane curvature | epithelial tubes

Topological Sound and Flocking on Curved Surfaces

“…In many biological processes, cell motion takes place on curved surfaces, as in cell renewal and repair in the highly folded intestine [85] and the shaping of the early limb bud in developing embryos [86]. The effect of curvature on the dynamics of epithelial cells is beginning to be explored in vitro by examining collective cell migration on cylindrical capillaries of varying radii [21]. While cylinders have zero Gaussian curvature, which would not yield topologically protected states, these experiments clearly demonstrate that curvature affects cell morphology and dynamics by enhancing cell speed and cell extrusion.…”

“…Recent in vitro work has demonstrated a direct effect of substrate curvature on cytoskeletal alignment and cell motility in epithelial cells [21]. Understanding the behavior of active matter on curved surfaces or confined by curved boundaries is therefore timely.…”

Modeling collective cell migration in geometric confinement

“…An interesting observation was made in [16] (and more recently in [18]), where the cell monolayer was found to propagate faster within the thinner stripes. This observation has remained an open puzzle ever since, and we aim to explain it in this paper.…”

Third harmonic generation microscopy of cells and tissue organization

“…This suggests a predominantly tissue-guided migration that is dictated by physical principles, including haptotaxis and contact guidance. By depicting the complexity of structural microenvironments in vivo, that study also provides the basis for bio-inspired engineered microdevices to probe cell migration in defined environments that simulate space restrictions, surface topography and geometry in the physiological range encountered by cells in tissues (Stroka et al, 2014;Yevick et al, 2015). Taken together, THG combined with SHG-or fluorescence-based microscopy can provide important anatomical context in three dimensions and so yield a framework of cause-consequence relationships in tumor progression, cell migration and the associated remodeling of the microenvironment.…”