Non-enzymatic oligonucleotide ligation in photoswitchable coacervate protocells sustains compartment-content coupling

Modern cells are adaptive chemical compartments tightly regulated by an underlying DNA-encoded program. Reproducing such a coupling between information content and chassis in synthetic compartments represents a key step to the assembly of evolvable protocells, but remains challenging. Here, we rationally exploit complexation between end-reactive oligonucleotides able to stack into long physical polymers and a cationic azobenzene photoswitch to produce three different phases – soft solids, liquid crystalline or isotropic coacervates droplets – that promote non-enzymatic oligonucleotide ligation, with a marked phase-dependent reaction efficiency. Changes in the population of polynucleotides during polymerization induce in turn phase transitions that dramatically alter the physical properties of the compartments. Dynamical modulation of coacervate assembly and dissolution via trans-cis azobenzene photoisomerisation is last used to demonstrate cycles of light-actuated oligonucleotide ligation. Overall, by combining a tight reaction-structure coupling and environmental responsiveness, our light-responsive reactive coacervates provide a novel general route to the non-enzymatic synthesis of polynucleotides, and pave the way to the emergence of a primitive genotype-phenotype coupling in membrane-free protocells.