Sticking together: Harnessing cadherin biology for tissue engineering

Directing cell behavior and building a tissue for therapeutic impact is the main goal of regenerative medicine, for which scientists need to modulate the interaction of cells with biomaterials. The focus of the field thus far has been on the incorporation of cues from the extracellular matrix but we propose that scientists take lessons from cell-cell adhesion proteins, more specifically cadherin biology, as these proteins make multicellularity possible. In this perspective, we re-examine cadherins through the lens of a tissue engineer for the purpose of advancing regenerative medicine. Furthermore, we summarize exciting developments in biomaterials inspired by cadherins and discuss some challenges and opportunities for the future. STATEMENT OF SIGNIFICANCE: Tissue engineers need tools to direct cell behavior. To date, tissue engineers have designed many sophisticated materials to positively influence cell behavior but are faced with the challenge where these materials sometimes work and sometimes fail. This uncertainty is a big unanswered question that challenges the community. We propose that tissue engineering could be more successful if they would take lessons from cell-cell adhesion proteins, more specifically cadherin biology. In the article, we discuss key structural and functional characteristics that make cadherins ideal for tissue engineering approaches. Furthermore, by providing a state-of-the-art overview of exemplary studies that have used cadherins to influence cell behavior, we show tissue engineers that they already have the tools necessary to incorporate this knowledge.