Cell-cell interactions are mediated through compositions expressed on the membrane. Engineering the cell surface to display functional modules with high biocompatibility, high controllability, and high stability would offer great opportunities for studying and manipulating these intercellular reactions. However, it remains a technical challenge because of the complex and dynamic nature of the cell membrane. Herein, by using three-dimensional (3D) amphiphilic pyramidal DNA as the scaffold, we develop a biocompatible, effective, and versatile strategy for engineering the cell surface with DNA probes. Compared with linear DNA constructs, these pyramidal probes show higher (nearly 100-fold) membrane-anchoring stability and higher (about 2.5-fold) target accessibility. They enable specific, effective, and tunable connections between cells. Meanwhile, our results indicate that connecting cells in close proximity are critical to initiate intercellular communication. By combining high programmability and high diversity of DNA probes, this strategy is expected to provide a powerful and designable membrane-anchored nanoplatform for studying multicellular communication networks.