Cells can fuse together to form larger, multinucleate cells called syncytia. These multinucleate cells can be pathological, such as the syncytia formed from viral infections like SARS-CoV-2, or advantageous, such as the fused cells that facilitate wound-healing or the single-cell barrier within the human placenta. In these examples, syncytia span an enormous size range. Wound-driven syncytia incorporate two or three nuclei and have an area of around 100 μm 2 ; the syncytia in the placenta grows to incorporate billions of nuclei with an area of over 10 m 2 during the course of pregnancy. How do these large cells maintain their shape, function, and integrity across these lengthscales while coexisting within a tissue of mononucleate cells? To explore the structure and reorganization of large cells, we fuse modified MDCK cells to create syncytia. In this talk, I will discuss ongoing work to characterize the response of syncytia to crowding within a tissue, the robustness of syncytia as a barrier, and the large-scale reorganization of syncytia over time.