Population stability risks and biophysical benefits of cell-cell fusion in macrophage, osteoclast, and giant multinucleated cells

Plant and animal cells are commonly understood as acquiring specialized functions through differentiation and asymmetric division. However, unique capabilities are also acquired when two or more cells fuse together, mixing cytoplasmic and genetic material. Here, we combine imaging experiments with biophysical modeling to perform the first risk-benefit analysis of cell-cell fusion. On one hand, we find fusion introduces an intrinsic instability to the population dynamics. On the other hand, we measure an unusual physiological scaling suggesting these cells grow substantially larger at lower energetic costs. Further analysis of the cytoskeleton finds a size-associated phase separation of F-actin that self-organizes multinucleated cell phenotypes.