Interaction dynamics between epithelial cysts captured by tissue rheology

Epithelial cysts are minimal structures involved in morphogenesis. They are fluid-filled cavities surrounded by an epithelial monolayer. During development, cyst grow and their interactions shape organs. While their growth dynamics as single structures are well characterized, physical mechanisms underlying their interaction remain poorly understood. Here, we design a minimal assay of interacting cyst doublets based on microfabrication, quantitative biology, and theory to show that Madin-Darby canine kidney (MDCK) cysts interaction is essentially determined by rheological properties of their epithelial monolayers. We report two phases of interaction: coalescence of cellular monolayers and lumen fusion, with similar speeds of 0.3 μm/h. We modulate the distribution of interaction phenotypes by reducing cell-cell adhesion using E-cadherin knock-out MDCK cells, and we report that E-cadherin depletion promotes lumen fusion. Remarkably, dynamics of coalescence and fusion are conserved between both cell lines. To understand the conserved speeds and the effect of cell-cell adhesion, we model the mechanical behavior of cyst doublets as a complex fluid to predict a speed determined by viscosity, stretch-dependent monolayer tension, and adhesion energy between cells. We measure these parameters through rheological experiments using micropipette aspiration and lumen drainage, spanningthe full range of stretch. A key insight from this analysis is that accounting for tension's dependence on stretch is essential to capture dynamics observed during cyst interaction. Using these rheological measurements, we successfully recapitulate the conserved speed. We show that Caco-2 cyst interactions follow similar rules. Altogether, our results open perspectives to understand tissue dynamics during organogenesis through simple physical arguments.