Generation of a cellular Yin-Yang pattern

Here we report dynamic pattern generation in a microengineered, model tissue system. When two or three bovine capillary endothelial cells (BCEs) were constrained to a square adhesive island (≤ 50 × 50 μm) coated with fibronectin (FN), coordinated cell migration resulted leading to stable rotation of the entire multicellular system about its geometric center. Each cell in this dynamic pattern was led by a lamellipodium that wrapped around the trailing edge of the neighboring cell, thereby creating a static form reminiscent of the Yin-Yang (YY) symbol of the Tao religion. When single cells were constrained to these islands they exhibited "edge-seeking" behavior: the leading edge of the cell preferentially migrated along the island perimeter. This behavior stopped when the cells fully spread and assumed the square shape of the island. Similar edge-driven motility was observed in creation of the multicellular YY pattern, however, this behavior persisted. Thus, the stable YY pattern emerged from collective behavior among the different interacting cellular elements. These observations suggest that a defined adhesive field may be capable of inducing complex pattern formation in tissues by spatially coupling mechanochemical processes that mediate cell migration.