An in situ Dynamic Continuum of Supramolecular Phosphoglycopeptides Enables Formation of 3D Cell Spheroids

Higher-order assemblies of proteins, with a structural and dynamic continuum, is a new paradigm in biology, but these insights have yet to be applied in designing biomaterials. Dynamic assemblies of supramolecular phosphoglycopeptides (sPGPs) transform a 2D cell sheet to 3D cell spheroids. A ligand-receptor interaction between a glycopeptide and a phosphopeptide produces sPGPs that form nanoparticles, which transform to nanofibrils upon partially enzymatic dephosphorylation. The assemblies form dynamically and hierarchically in situ on the cell surface, and interact with extracellular matrix molecules and effectively abolish contact inhibition of locomotion (CIL) of the cells. Integrating molecular recognition, catalysis, and assembly, these active assemblies act as a dynamic continuum to disrupt CIL, thus illustrating a new kind of biomaterials for regulating cell behavior.