Multi-tissue mosaics of homotypic and heterotypic cell monolayers*

We developed a framework for predicting the interaction of multiple expanding cell monolayers that fuse into one large monolayer. Individual epithelial monolayers expand at a constant outward speed and thus the evolution of their shapes can be predicted using the Huygens principle. To quantify tissue interactions, we investigated collisions of pairs of homotypic epithelial monolayers with different tissue shapes, densities, and sizes. Upon tissue collisions, their boundaries can move by a few cell lengths but they eventually “freeze” due to the contact inhibition of locomotion. For collisions of three tissues, we sometimes observe very narrow planar extrusions, when one of the tissues reaches high enough migration speed to stay ahead of the other two converging tissues. Based on these observations, we developed a computational model to predict the evolution of multi-tissue mosaics by using the Huygens principle of expanding tissues, whose boundaries freeze upon collisions. Without any fitting parameters, this model accurately predicts large scale morphology of multi-tissue mosaics of homotypic and heterotypic cell monolayers, where the mismatch of migration speeds for different cell types can lead to phenomena like total engulfment.