Biosynthesis-Integrated Editing of Bacterial Cellulose Enables Sequence-Programmable Biointerfaces

Abstract Structural polysaccharides self-assemble into densely packed fibrils, providing a molecular foundation for the hierarchical organization and mechanical integrity of biological materials. However, the same interchain interactions that stabilize these structures severely restrict chemical accessibility, making molecular editing after assembly a formidable challenge. Here, we integrate regiochemical editing into bacterial cellulose biosynthesis using azido-glucose analogues substituted at C2, C3, or C6. The resulting cellulose materials exhibit regioisomer-dependent differences in crystallinity, fibrillar organization, and mechanical properties, while precursor feeding further modulates crystallinity. The incorporated azide groups remain chemically accessible after assembly, enabling DNA conjugation and rolling-circle amplification to construct sequence-programmable aptamer interfaces. By varying the aptamer sequence, the same cellulose platform can be reprogrammed for either selective cell capture and release or HGF-mimetic regulation of endothelial behavior. This work establishes a biosynthesis-integrated strategy that connects molecular editing during cellulose formation with hierarchical material organization and subsequent biological programming.