U2OS cells and other epithelial lines exhibit significant contact inhibition of migration in culture. When two or more of the cells collide, the membrane ruffling along their shared margins generally ceases and the cells appear to stick together. Sometimes continued lamellipodia ruffling along the free edges of the cells enable them to release their adhesions with one another, allowing them to commence independent migration in different directions. More commonly, however, epithelial cells remain tethered together as part of a growing colony, several of which may join together to form an epithelial sheet.

Characteristic epithelial cell behavior is demonstrated by the human osteosarcoma cells presented in this time-lapse sequence. At the beginning of the video, a pair of connected U2OS cells is situated on the surface of the imaging chamber in close proximity to a large colony of the epithelial cells. The ruffling lamellipodia along the margins of the cells reach out across the substratum and adhere to a nearby cell along the left-hand side of the field of view, as well as cells comprising party of the growing U2OS cell colony. Many additional cells produced via mitosis further expand the colony, and by the end of the video an almost contiguous monolayer is formed.

The behavior of the cultured U2OS cells is thought to be a reflection of the natural behavior of epithelial cells in the body. When a wound occurs on the surface of the skin, for example, epithelial cells along the edges of the injured area extend lamellipodia out in an attempt to form a continuous epithelial sheet across the lesion. When the lamellipodia reach other cells and the sheet is successfully produced, the large-scale movements of the cells ceases and specialized junctions are created between the newly adjacent cells.