Mechanistic Insights into the Phase Separation Behavior and Pathway‐Directed Information Exchange in all‐DNA Droplets

Liquid‐liquid phase separation provides a versatile approach to fabricating cell‐mimicking coacervates. Recently, it was discovered that phase separation of single‐stranded DNA (ssDNA) allows for forming protocells and microgels in multicomponent systems. However, the mechanism of the ssDNA phase separation is not comprehensively understood. Here, we present mechanistic insights into the metal‐dependent phase separation of ssDNA and leverage this understanding for a straightforward formation of all‐DNA droplets. Two phase separation temperatures are found that correspond to the formation of primary nuclei and a growth process. Ca(2+) allows for irreversible, whereas Mg(2+) leads to reversible phase separation. Capitalizing on these differences makes it possible to control the information transfer of one‐component DNA droplets and two‐component core–shell protocells. This study introduces new kinetic traps of phase separating ssDNA that lead to new phenomena in cell‐mimicking systems.