Classic ‚Äòwound healing‚Äô studies in cell monolayers use a wound or barrier removal to induce and study collective migration, focusing on the migration rather than the ultimate collision and tissue healing. Here, we address this by comprehensively studying monolayer tissue-tissue interactions in homotypic and heterotypic tissues from the initial outgrowth of separated tissues up to collision and for many hours afterward. We show that the size, shape, and density of the initial tissues causes the boundary to vary over time by several cell lengths until the newly fused tissue stabilizes after 2-3 cell cycles. In the case of heterotypic tissues, differences in cell type become very important. For example, we show that a more rapidly expanding tissue overtakes and engulfs a slowly expanding tissue, providing an in vitro analogy to envelopment processes important in development. In addition to characterizing interactions and boundary dynamics between colliding tissues, we predict the resulting fused tissue forms using a simple-parameter computational model assuming outward growth at constant edge speed, which is used to systematically design the final resulting ‚Äúmosaic‚Äù from many growing tissues. This model also accurately describes the final forms resulting from the rapidly expanding tissue engulfing a slowly expanding tissue. Finally, we show that unexpected boundary dynamics occur at the confluence of three or more tissues coming together that can lead to surprising planar extrusions where one tissue pushes out between converging neighboring tissues resulting in long, stretched regions of tissues.
*Work was supported by NIH grant R35 GM133574-01.


Tissue-tissue interactions at the boundaries of colliding expanding cell monolayers

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