Fueling DNA Self-Assembly via Gel-Released Regulators.

The development of responsive, multicomponent molecular materials requires means to physically separate yet easily couple distinct processes. Here we demonstrate methods to use molecules and reactions loaded into microliter-sized polyacrylamide hydrogels (mini-gels) to control the dynamic self-assembly of DNA nanotubes. We first characterize the UV-mediated release of DNA molecules from mini-gels, changing diffusion rates and minimizing spontaneous leakage of DNA. We then demonstrate that mini-gels can be used as compartments for storage and release of DNA that mediates the assembly or disassembly of DNA nanotubes in a one-pot process and that the speed of DNA release is controlled by the mini-gel porosity. With this approach, we achieve control of assembly and disassembly of nanotubes with distinct kinetics, including a finite delay that is obtained by loading distinct DNA regulators into distinct mini-gels. We finally show that mini-gels can also host and localize enzymatic reactions, by transcribing RNA regulators from synthetic genes loaded in the mini-gels, with diffusion of RNA to the aqueous phase resulting in the activation of self-assembly. Our experimental data are recapitulated by a mathematical model that describes the diffusion of DNA molecules from the gel phase to the aqueous phase in which they control self-assembly of nanotubes. Looking forward, DNA-loaded mini-gels may be further miniaturized and patterned to build more sophisticated storage compartments for use within multicomponent, complex biomolecular materials relevant for biomedical applications and artificial life.