Confinement-Induced Fractionation and Liquid–Liquid Phase Separation of Polymer Mixtures

The formation of (bio)molecular condensates via liquid–liquid phase separation in cells has received increasing attention, as these aggregates play important functional and regulatory roles within biological systems. However, the majority of studies focused on the behavior of pure systems in bulk solutions, thus neglecting confinement effects and the interplay between the numerous molecules present in cells. To better understand the physical mechanisms driving condensation in cellular environments, we perform molecular simulations of binary polymer mixtures in spherical droplets, considering both monodisperse and polydisperse molecular weight distributions for the longer polymer species. We find that confinement induces a spatial separation of the polymers by length, with the longer ones moving to the droplet center. This partitioning causes a distinct increase in the local polymer concentration near the droplet center, which is more pronounced in polydisperse systems. Consequently, the confined systems exhibit liquid–liquid phase separation at average polymer concentrations where bulk systems are still in the one-phase regime.