A thermodynamic study of condensate formation in a mixture of DNA-binding protein from starved cells (Dps) and DNA

The DNA-binding protein from starved cells (Dps) is essential for bacterial survival under stress. As a nucleoid-associated protein, Dps interacts with DNA to form biomolecular condensates in living bacteria. In vitro, purified Dps rapidly form stable complexes with DNA, which is key in nucleating and stabilizing the condensates. To investigate this, we examine the phase behavior of a ternary mixture of DNA, Dps, and solvent using the Flory-Huggins (FH) free energy model. We obtain relevant phase diagrams using the stability analysis of a ternary FH free energy landscape. We identify the binodal (condensate forming) regions and their evolution as functions of the concentrations of Dps and DNA, and the interactions between Dps, DNA, and solvent. Condensate stability increases with stronger mutual attraction between Dps and DNA and weaker self-repulsion between individual Dps and DNA molecules for moderate solvent interactions. This mean-field thermodynamic framework complements molecular simulations, which offer additional insights into the structure and molecular ordering in Dps-DNA condensates as functions of intermolecular interactions.