Different states and the associated fates of biomolecular condensates

Biomolecular condensates are functional assemblies, which can enrich intrinsically disordered proteins (IDPs) and/or RNAs at concentrations that are orders of magnitude higher than the bulk. In their native functional state, these structures can exist in multiple physical states including liquid-droplet phase, hydrogels, and solid assemblies. On the other hand, an aberrant transition between these physical states can result in loss-of-function or a gain-of-toxic-function. A prime example of such an aberrant transition is droplet aging-a phenomenon where some condensates may progressively transition into less dynamic material states at biologically relevant timescales. In this essay, we review structural and viscoelastic roots of aberrant liquid-solid transitions. Also, we highlight the different checkpoints and experimentally tunable handles, both active (ATP-dependent enzymes, post-translational modifications) and passive (colocalization of RNA molecules), that could alter the material state of assemblies.