Dynamic Switchable and Transient DNA Condensates Driven by Aptamer‐Ligand or Ion‐Nucleobase Bridged Complexes

Phase-separated DNA-based coacervates undergoing dynamic switchable or transient evolution and depletion are introduced. Y-shaped DNA reaction modules crosslinked by palindromic strands conjugated to cooperatively stabilized metal-ions/mismatched bridges, C-Ag+-C or T-Hg2+-T, evolved phase-separated microdroplets. Removal of the bridging ions by cysteamine (MEA) for Ag+ or dimercaptosuccinic acid (DMSA) for Hg2+ separates the condensates. Cyclic treatment of Y-shaped modules and the palindromic strands with Ag+/Hg2+, and the subsequent ligands MEA/DMSA, result switchable formation/dissociation of the condensates. In addition, crosslinking of Y-shaped DNA reaction modules with palindromic strand, and cooperatively stabilized or destabilized by aptamer/ligand complexes, leads, in the presence of an auxiliary biocatalyst, separating the ligand/aptamer complexes, to the transient evolution/depletion of the condensates. This is exemplified with the adenosine-induced phase-separation of condensates by crosslinking of aptamer subunit-modified Y-shaped modules with palindromic strands cooperatively stabilized by adenosine/aptamer-subunits. In the presence of adenosine deaminase (ADA), transforming adenosine to inosine, the transient, dissipative depletion of the condensates proceeds. Alternatively, crosslinking of DNA Y-shaped modules with palindromic strands conjugated to adenosine aptamer units, leads to the evolution of phase-separated adenosine-responsive microdroplets. In the presence of adenosine and ADA, the transient depletion of the microdroplets and their dynamic temporal reassembly proceeds.