A Simple Model to Predict Complex Coacervation: Forces as Drivers of Phase Change and Structuration

Résumé fourni par la source

Biomolecular condensate formation or coacervation has come to the fore as an extremely attractive research area over the past few years, as these condensates have been conjectured to be the most primitive sort of protocells. One of the most studied coacervation process is the complex coacervation between polyelectrolytes and oppositely charged small molecules. Among these structures, a very well tested system is the poly-L-Lysine/Adenosine Tri Phosphate (pLL/ATP) coacervate. To understand the condensation process, one needs to unravel the forces which dictate the behaviour of pLL dispersed in water at various temperatures and for various monomer charge fractions which are positively charged. Unlike most simulations which have been performed for biologically relevant proteins, here we have used an included solvent Monte Carlo approach on 10-bead flexible strands as the model pLL molecules, where each bead stands for 3 lysine monomers. Initially we have established the 10-bead model for pLL molecules. We have shown that at high pH, when the positive charges are largely neutralized due to deprotonation of the amine groups in the lysine monomers, the strands show a clear tendency to form bundles of rigid and vertically elongated pLL molecules driven by intermolecular attractions caused by hydrophobic repulsion from the aqueous medium. On switching off the hydrophobic interaction, we see no bundle formation and the screened coulomb repulsions dominate pushing the strands away from each other, underscoring the essential role of hydrophobic interaction in pLL structuration. We see a similar tendency to move away from each other by keeping the charges fixed at high reduced temperatures as well. These results agree nicely with experimental observations of the different phases of pLL, in particular the formation of fibrils at high pH and room temperature. Once we established the pLL model, we introduced negatively charged single ATP beads. Based on the screened coulomb attractions between the polymers and the molecules, we could predict the crossover point where the repulsive regime gets converted into an overall attractive one leading to nucleation and growth, resulting into coacervation. We could, therefore, correlate the ATP/pLL ratio to the forces dictating the phase separation process – for the first time to the best of our knowledge. Additionally, we could find the radial charge and ATP and pLL bead density distributions which allows us to understand the internal structures of the condensates.

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