Jie Zhou, Xuewen Du, Xiaoyi Chen, Bing Xu

Despite the well-established biophysical principle of adhesion-guided in vitro morphogenesis, there are few single syn-thetic molecular species that can rapidly enable morphogenesis (e.g., a cell monolayer to cell spheroids) in cell culture because adhesion process inherently involves many signals. Here we show the use of adaptive multifunctional supramo-lecular assemblies of glycopeptides, consisting of cell adhesion sequence and saccharide, to induce cell spheroids rapid-ly from a monolayer of cells. Having a general architecture of N-terminal capping, glycosylation, and an integrin bind-ing sequence, the glycopeptides self-assemble to form a dynamic continuum of nanostructures (i.e., from nanoparticles to nanofibers) to affect the interactions of integrins, E-selectin, and cadherins with their natural ligands and to act adaptively according to cellular environment. Such adaptive (i.e., context-dependent) interactions reduce cell-substratum adhesion and enhance intercellular interactions, which rapidly and transiently induce cell spheroids. This work illustrates a new approach that uses supramolecular assemblies of simple glycopeptides as molecular modulators of biophysical condition of cells for understanding and affecting cell functions in the development of supramolecular biomaterials.