Mechanics and polarization of large syncytial cells across length scales

Syncytia, multinucleated cells, appear in a variety of biological systems, yet our understanding of their underlying mechanics compared to their mononuclear counterparts remains poorly understood. At one extreme, small syncytia can expedite the wound healing process, and at the other extreme, the syncytiotrophoblast, containing approximately 60 billion nuclei, acts as the primary barrier between fetal and maternal blood within the placenta. MDCK cells expressing the viral fusogen hemagglutinin provide a robust in vitro model for syncytia at extreme size scales. We employ migration assays to gain an understanding of how syncytia organize and polarize in a mononuclear epithelium under a stress gradient. We identified that syncytial movement and polarization depends on cell size. Traction force experiments reveal how a syncytia's internal stresses differ from mononuclear islands of similar surface areas. Our work provides insight into how cell size impacts syncytial mechanics across length scales.