Unraveling the Entropic Influence of Crowded Environments on the Structure of Coacervate Droplets

Solidification of protein condensates (e.g., stress granules) has been linked to various neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The genesis of these condensates is a form of liquid-liquid phase separation (LLPS) and the transition from viscous fluid to viscoelastic gel-like state has been observed to be dependent on crowding environment. Although experimental findings predict the entropic effects due to crowded solvent environment plays a major role in affecting the condensate formation and its internal structure, molecular-level evidence supporting these effects is scarce. We use molecular dynamics applied to LLPS in a system of polyelectrolytes (PEs) to explore the effects of crowding in a model incorporating explicit solvent molecules and crowders of varying molecular weight. We find the crowded environment alters phase separation temperature, compactness and excess pair entropy, presenting an excellent starting point for explaining experimental results.