Surface-Initiated PET-RAFT Enables In Situ Glycopolymer Microarrays for Live-Cell Glycan Profiling and Programmable Biointerfaces

Glycopolymer microarrays offer a powerful route to probe glycan-protein interactions, but existing "grafting-to" approaches require presynthesized polymers and provide limited control over surface density and multivalent presentation. Here we introduce a surface-initiated photoinduced electron-transfer RAFT (SI-PET-RAFT) platform that enables the in situ growth of well-defined glycopolymers directly on solid substrates under mild, oxygen-tolerant conditions. Using a combinatorial library of glycopolymers, we mapped the binding preferences of live HepG2, RAW264.7, and HeLa cells, revealing distinct and composition-dependent glycan-recognition signatures driven by multivalent effects. Guided by these insights, we designed thermoresponsive glycopolymer brushes on 96-well plates that mediate selective HepG2 adhesion at 37 °C and rapid, nondestructive release at 4 °C. This integrated workflow links high-throughput glycopolymer screening to the rational engineering of functional biointerfaces, offering broad opportunities in diagnostics, cell sorting, and glycan-targeted biomaterial design.