Cyto-friendly polymerization at cell surfaces modulates cell fate by clustering cell-surface receptors

Lots of strategies, e.g. using multivalent synthetic polymers, have been developed to control the spatial distribution of cell-surface receptors, thus modulating the cell function and fate in a custom-tailored manner. However, clustering cell-surface receptors via multivalent synthetic polymers is highly dependent on the structure as well as the ligand-density of the polymers, which may impose difficulties on the synthesis of polymers with a high density of ligands. Here, we pioneered the utilization of a cyto-friendly polymerization at the cell surface to cluster cell-surface receptors. As a proof of concept, an anti-CD20 aptamer conjugated macromer was initially synthesized, which was then efficiently and stably introduced onto the Raji cell surface via ligand-receptor interaction. With the assistance of an initiator, i.e. ammonium peroxysulfate (APS), the macromer bound onto the Raji cell surface polymerized, inducing the clustering of CD20 receptors, and thereby triggering cell apoptosis. This cell-surface polymerization induced cell-surface receptor crosslinking could alternatively be applied in modulating the fates and functions of other cells, especially those mediated by the spatial distribution of cell-surface receptors, such as T cell activation. Our work opens new possibilities in the area of chemical biology to some extent.