Entropy-driven phase behavior of all-DNA associative polymers

Associative polymers (APs) with reversible, specific interactions between “sticker” sites exhibit a phase behavior that depends on a delicate balance between distinct contributions controlling the binding. For highly bonded systems, it is entropy that mostly determines whether, upon increasing concentration, the network forms progressively or via a first-order transition. With the aim of introducing an experimentally viable system tailored to test the subtle dependence of the phase behavior on binding site topology, we numerically investigate APs made of DNA, where “sticker” sites formed by short DNA sequences are interspersed in a flexible backbone of poly-T spacers. Due to their self-complementarity, each binding sequence can associate with another identical sticky sequence. We compare two architectures: one with a single sticker type, (AA)6, and the other with two distinct alternating types, (AB)6. At low temperatures, when most of the stickers are involved in a bond, the (AA)6 system remains homogeneous, while the (AB)6 system exhibits phase separation, driven primarily by entropic factors, mirroring predictions from simpler bead-spring models. Analysis of bond distributions and polymer conformations confirms that the predominantly entropic driving force behind this separation arises from the different topological constraints associated with intra- vs inter-molecular bonding. Our results establish DNA APs as a controllable and realistic platform for studying in the laboratory how the thermodynamics of associative polymer networks depend on the bonding site architecture in a clean and controlled manner.