In Situ DNA Self-Assembly on the Cell Surface Drives Unidirectional Clustering of Membrane Proteins for the Modulation of Cell Behaviors

Cell membrane proteins play a pivotal role in regulating intracellular signal transductions and cell behaviors. Many membrane proteins form clusters in order to initiate downstream signaling pathways for the modulation of cell behaviors. Developing rational methods to program the in situ clustering of designated membrane proteins on the cell surface to form large assemblies remains challenging. Here we use the membrane-anchored DNA hybridization chain reaction (HCR) to induce DNA self-assembly on the live cell surface and drive the unidirectional clustering of membrane proteins for the modulation of cell behaviors. Reactive DNA strands are specifically anchored onto the membrane proteins of interest by using DNA aptamers. Upon activation, the chain reaction between the protein-anchored DNA strands drives the assembly of membrane proteins forming one-dimensional clusters. We demonstrate both homogeneous and heterogeneous clustering of membrane proteins on multiple cell types that exhibit a potent capability for modulating cell behaviors including migration, proliferation, and survival.