DNA-based hydrogels as tunable scaffolds for cell mechanobiology

The study of cell-matrix interactions is fundamental for understanding cell biology, disease progression, advancing tissue engineering and regenerative medicine. However, these studies require sophisticated substrates to mimic the effect of the cellular microenvironment in vitro. In this context, hydrogels have emerged as promising biomaterials due to their ability to approach natural tissue environments. [1,2] Among these, DNA-based hydrogels have garnered significant attention because of the intrinsic properties of DNA, including biocompatibility, programmable self assembly, and tunable mechanical properties. [3,4] To develop innovative scaffolds for 2D and 3D cell culture, we have employed two types of genomic DNA with varying sequences and lengths, in different aqueous media. We studied the chiroptical properties of genomic DNA in both aqueous solutions and gel states, and measured the Young’s modulus of hydrogels using microindentation techniques. Our results show that the chiroptical properties of DNA in solution and gel states are similar, suggesting that the hydrogels primarily consist of large portions of double-stranded DNA. Additionally, our results indicate that the stiffness of the gels falls within the kPa range, with the Young’s modulus varying from 1 kPa to 8 kPa depending on the DNA concentration. These hydrogels present promising scaffolds for studying cell migration, with the advantage of tunable mechanical properties in the kPa range.