DNA origami as a biomaterials platform for programming ligand-receptor interactions and cell fate.

DNA origami has emerged as a versatile biomaterials platform enabling programmable control over the nanoscale spatial organization of ligands. Unlike conventional biomaterials platforms, which offer limited geometric precision, DNA origami allows systematic engineering of key parameters-including ligand valency, inter-ligand spacing, and nanopatterning-with single-molecule accuracy. This minireview summarizes the key advances over the past five years in employing DNA origami-based biomaterials to modulate membrane receptor activation, downstream signaling, and cellular fate decisions. We discuss how engineered ligand nanotopology serves as a spatial switch to decode receptor activation thresholds, orchestrate multi-receptor synergy, and achieve biomimetic antigen presentation. Furthermore, we highlight the translational potential of these platforms in immunotherapy, targeted drug delivery, and vaccine development. Finally, we offer perspectives on engineering next-generation intelligent DNA biomaterials for cross-scale biological regulation, bridging nanoscale ligand design with tissue-level therapeutic outcomes.