Programming Multicellular Assembly with Synthetic Cell Adhesion Molecules.

Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions in processes as diverse as tissue development, immune cell trafficking, and wiring of the nervous system. 1-4 Here, we show that a wide array of synthetic cell adhesion molecules (synCAMs) can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell-cell interactions with adhesion properties similar to native interactions. The synCAM intracellular domain identity dominates in specifying interface morphology and mechanics, while diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables rationally programmed assembly of novel multicellular architectures, as well as systematic remodeling of native tissues. The modularity of synCAMs provides fundamental insights into how distinct classes of cell-cell interfaces may have evolved. Overall, these tools offer powerful new capabilities for cell and tissue engineering and for systematically studying multicellular organization.