Noncovalently Bridging Cell-Surface Proteins Using Synthetic Peptides to Modulate Cell Apoptosis

Controlled high-order clustering of cell-surface proteins is an essential but unmatched regulatory mechanism in living systems for the modulation of cell behavior. Here, we present a strategy for generating extended and tunable one-dimensional clusters of death receptors on live cell surfaces by employing synthetic peptides to noncovalently bridging the proteins. The on-cell assembly process is validated through super-resolution fluorescence imaging and fluorescence lifetime imaging analyses. By adjusting the number of spacing peptides between the receptors before and even after the cluster formation, receptor separation can be precisely varied at nanoscale to drive cells into apoptotic or antiapoptotic states. Remarkably, this approach results in higher levels of cell apoptosis compared to the conventional practice of using preformed ligand-appended peptide coassemblies. These results demonstrate that in situ fabrication of cell-interfacing materials with compositional control permits robust and effective manipulation of high-order clustering of cell-surface proteins, advancing our ability to regulate cell behavior.