Interchain base-stacking and spermine bridges govern ssDNA condensation and reentrant transitions
Year: 2026
Type: preprint
Abstract: Polyvalent-cation-induced condensation and reentrant transition in double-stranded DNA are classically described by backbone electrostatics. Whether the same principles govern single-stranded DNA, whose solvent-exposed bases can interact within and between chains to form complex phases, is unknown. Here, we employ simulations and experiments to show that the tetravalent cation spermine (Spm 4+ ) drives two equilibrium transitions in poly(dT) and poly(dA). The onset of phase separation, resulting in thermodynamic equilibrium between the dispersed low-density phase and high density coacervate, occurs at a low sequence independent Spm 4+ concentration and is primarily driven by charge balance between phosphate groups and Spm 4+ . Strikingly, the condensed phases are stabilized by at most 1.5 (polydT) and 2.5 (polydA) bridging Spm 4+ per chain. The ssDNA chains condense to form fluid-like networks without chain collapse . The fluidity of chains in the dense phases is confirmed by fluorescence recovery after photobleaching experiments. Both simulations and experiments show that the range of spermine concentration over which phase coexistence persists is sequence dependent and nearly threefold wider in poly(dA). At higher sequence dependent spermine concentrations, a reentrant phase, characterized by dissolution of the coacervates, emerges. The transition to the reentrant phase occurs when the number of bridging Spm 4+ molecules vanishes at high sequence dependent spermine concentration. The combination of experiments and simulations show that the two phase transitions in ssDNA are driven by an interplay of stacking and electrostatic interactions.
Language: English
Subfield: Physical and Theoretical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7220983495