Cell adhesion molecules (CAMs) are ubiquitous in multicellular organisms and specify precise cellular interactions in processes as diverse as tissue development and immune cell trafficking. We have generated an array of synthetic CAMs by combining orthogonal extracellular interactions with native intracellular domains. Diverse homotypic or heterotypic extracellular binding domains specify the connectivity between cells, while the intracellular domain identity dictates interface morphology and mechanics. This approach highlights CAM modularity and enables rationally programmed assembly and remodeling of multicellular architectures. Overall, these tools offer new customizable capabilities for cell and tissue engineering and for systematically studying multicellular organization.