The behavior of MDBK cells and other epithelial lines in culture is distinctly different in some regards than the behavior of fibroblast cells. Most notably, epithelial cells are much more strongly contact inhibited, frequently binding together to form small colonies rather than migrating across the substratum independently, as is common among fibroblasts. This epithelial cell tendency is reflective of the primary role epithelial cells play in the body, where they form specialized junctions with neighboring cells to create epithelial sheets. The sheets, which cover most internal and external surfaces of the body and its organs, are crucial as barriers against the diffusion of molecules.

There tends to be little surface extension activity along the overlapping margins of adjacent cells. Consequently, MDBK cells in the center of a colony appear relatively stable, though they can still undergo shifts in shape and location. As demonstrated in this video, cells on the periphery of a colony, where they have at least one free margin, are significantly more dynamic. They continue to extend and retract broad, flattened lamellipodia, which often exhibit a fan-like shape.

The movements of lamellipodia appear rapid during the high speed playback of time-lapse sequences and can produce a flickering sensation. This phenomenon is known as ruffling and involves the extension, folding back, and return of the protrusion into the central region of the cell. The overall rearward movement of membrane ruffles causes any particles that adhere to the surface of a motile cell to be carried toward the back of that cell.