Programming multicellular interactions and organization using synthetic cell adhesion molecules

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 show that a wide array of synthetic CAMs can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield cell-cell connections with adhesion properties similar to native interactions. The intracellular domain identity dictates interface morphology and mechanics, while diverse homotypic or heterotypic extracellular binding domains specify the connectivity between cells. This toolkit highlights the modularity of cell adhesion molecules 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.