Viscoelastic and thermoreversible networks crosslinked by non-covalent interactions between “clickable” nucleic acid oligomers and DNA

Abstract

An approach to efficient and scalable production of oligonucleotide-based gel networks is presented. Specifically, a new class of xenonucleic acid (XNA) synthesized through a scalable and efficient thiol–ene polymerization mechanism, “clickable” nucleic acids (CNAs), were conjugated to a multifunctional poly(ethylene glycol), PEG. In the presence of complementary single stranded DNA (ssDNA), the macromolecular conjugate assembled into a crosslinked 3D gel capable of achieving storage moduli on the order of 1 kPa. Binding studies between the PEG-CNA macromolecule and complementary ssDNA indicate that crosslinking is due to the CNA/DNA interaction. Gel formation was specific to the base sequence and length of the ssDNA crosslinker. The gels were fully thermoreversible, completely melting at temperatures above 60 °C and re-forming upon cooling over multiple cycles and with no apparent hysteresis. Shear stress relaxation experiments revealed that relaxation dynamics are dependent on crosslinker length, which is hypothesized to be an effect of the polydisperse CNA chains. Arrhenius analysis of characteristic relaxation times was only possible for shorter crosslinker lengths, and the activation energy for these gels was determined to be 110 ± 20 kJ mol⁻¹. Overall, the present work demonstrates that CNA is capable of participating in stimuli-responsive interactions that would be expected from XNAs, and that these interactions support 3D gels that have potential uses in biological and materials science applications.