Mechanistic determinants of cellular biomolecular condensates

Determine how different molecular mechanisms influence the formation, regulation, and physical properties of biomolecular condensates (membrane-less organelles formed via liquid–liquid phase separation of macromolecules) in living cells, accounting for the complex and dynamic nature of the intracellular environment.

Background

The paper studies liquid–liquid phase separation (LLPS) with a focus on weak polyelectrolytes whose charge is regulated by local pH via protonation/deprotonation. It emphasizes that many biomacromolecules in cells are weak polyelectrolytes and that electrostatic interactions and charge regulation critically shape phase separation dynamics and the properties of condensed phases.

Despite advances in modeling and experiments on coacervation and biomolecular condensates, the authors note that understanding condensate formation and regulation in vivo remains challenging due to the complexity and dynamism of cellular environments. This motivates the explicit open challenge of determining how different molecular mechanisms contribute to condensate behavior within cells.