Work

DNA Framework Nucleator‐Enabled Intelligent Hydrogel Interfaces on Living Cells

Year: 2026

Type: article

Abstract: Engineering intelligent interfaces on living cells is essential for precise cellular manipulation. Here, we developed a DNA framework nucleator (DFN)-guided strategy for the controlled assembly of high-fidelity stimuli-responsive intelligent hydrogel interfaces (HIs) on living cell surfaces. Using a rigid tetrahedral DNA framework as the structural core, DFNs served as stable and ordered nucleation sites on the cell membrane, which directed localized branched hybridization chain reaction to form single-cell HIs. For ATP-responsive HIs, a response efficiency of ∼90.7% was achieved, representing an ∼2.9-fold enhancement over the HIs guided by a flexible double-stranded DNA nucleator (dsDN). Notably, this platform supports the integration of dual-locked and crosstalk-free logic gate function, triggering efficient disassembly exclusively when both ATP and microRNA-122 are present. This AND-gate function yielded a response efficiency of ∼98.5%, outperforming the dsDN-guided control by 4.2-fold, with a background crosstalk below ∼4.0%. These results demonstrate that ordered nucleation is essential for high-fidelity signal processing at cellular interfaces, advancing the field from static encapsulation to dynamic, logic-regulated systems and establishing a versatile platform for next-generation programmable cell-based applications.

Source: Small

DOI: 10.1002/smll.74016