Biomolecular condensate

Biomolecular condensates are specialized, membraneless compartments within cells that concentrate proteins and nucleic acids to organize biochemical reactions. These assemblies typically form through liquid-liquid phase separation (LLPS), a process driven by weak, multivalent interactions—most notably hydrophobic interactions, electrostatic forces, and cation-pi interactions—often involving intrinsically disordered regions (IDRs) of proteins (Banani et al., 2017; Shin & Brangwynne, 2017). Functionally, they serve as hubs for signal transduction, RNA processing, and stress responses, allowing the cell to compartmentalize activity without the need for lipid membranes (Alberti et al., 2019). In disease states, the physical properties of these condensates can shift from liquid-like to solid-like aggregates, a hallmark of neurodegenerative conditions such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer's disease (Patel et al., 2015). Furthermore, condensates can sequester or exclude therapeutic drugs, significantly impacting drug efficacy and resistance in cancer (Klein et al., 2020). Modern drug discovery efforts focus on condensate-modifying small molecules (c-mods) that can selectively dissolve pathological assemblies or alter the partitioning of therapeutic agents into specific cellular compartments.

Other names

Liquid-liquid phase separated dropletsMembraneless organellesLLPS condensatesStress granulesP-bodiesNuclear bodiesSignalosomes

Modulation of liquid-liquid phase separation (LLPS) dynamics, including the dissolution of pathological aggregates, alteration of protein partitioning, or stabilization of functional condensates.