Recent advances in mechanically programmable DNA hydrogels

DNA hydrogels are a programmable class of soft materials at the interface of chemistry, mechanics, and biology. Owing to their sequence-defined building blocks and reversible base-pairing interactions, these systems enable control over structure and dynamics across multiple length scales. Recent efforts have shifted toward understanding and engineering the mechanical properties of DNA hydrogels in biologically relevant environments, where stiffness, viscoelasticity, and adaptability regulate molecular and cellular processes. Here, we review advances in programming the mechanical properties of DNA hydrogels, focusing on how molecular rigidity, network topology, and dynamic crosslinking govern macroscopic properties. We discuss multiscale characterization strategies that connect single-molecule mechanics with bulk material behavior, and are beginning to yield structure-mechanics correlations. We highlight design approaches that decouple mechanical cues from chemical composition, providing platforms for probing mechanoregulation in biology. Finally, we outline the progression from empirical tunability to rational design and predictive frameworks for biomedical applications.