Peptide‐Peptide Nucleic Acid Hybrid Hydrogel Based on Sequence Programmable Morphological Change for DNA Data Storage

Peptide‐based hydrogels provide biocompatible, stimuli‐responsive platforms, while peptide‐DNA hybrids extend programmability through hybridization‐driven crosslinking. However, nucleobase incorporation can influence peptide self‐assembly pathways. We demonstrate that the introduction of bases can directly alter the transition of peptides between gel and solution, offering an alternative mechanism to hybridization‐dependent approaches. Using peptide nucleic acid–guanine as a molecular bridge, guanine attachment shifts peptide assemblies from gel to solution states. Conversely, introducing complementary cytosine‐rich DNA sequences triggers a solution‐to‐gel transition. This morphological switching is sequence‐specific, enabling precise spatiotemporal control of gelation. Structural and rheological analyses confirm guanine's critical role in altering peptide backbone organization and enabling dynamic reconfiguration. As a demonstration of this programmable material's capabilities, we applied the hydrogel for DNA data storage. The hydrogel protects encapsulated DNA information from enzymatic degradation and facilitates precise digital information retrieval, establishing a robust storage medium for synthetic DNA‐encoded data. This strategy leverages nucleic acid sequence specificity to directly manipulate peptide nanostructure, advancing the design of smart, stimuli‐responsive biomaterials.