Response of Large Multinucleated Cells to Crowding in MDCK Tissue

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 a wound-healing front. In both examples, the larger cells must maintain their shape, function, and integrity within a tissue of mononucleate cells. We explore the response and reorganization of syncytia within an increasingly dense tissue. We fuse modified MDCK cells to create large syncytia that coexist with mononucleate MDCK cells. The mononucleate cells continue to proliferate, increasing cell crowding over time. We characterize the resulting changes in the size, structure, and internal organization of the cells. We find that syncytia respond differently to crowding than mononucleate cells. We additionally observe large-scale internal reorganization of the syncytia within the tissue, which could contribute to the mechanical stability of the large cells over time.