Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates

Significance Cell instructive biomaterial cues are a major topic of interest in both basic and applied research. In this work, we clarify how surface energy of soft biomaterials can dramatically affect mesenchymal stem cell receptor recruitment and downstream signaling related to cell fate. We elucidate how surface protein self-assembly and the resulting surface topology can act to steer mechanotransduction and related biological response of attached cells. These findings fill a critical gap in our basic understanding of cell–biomaterial interaction and highlight soft biomaterial surface energy as a dominant design factor that should not be neglected.