Scaffold Affinity Tunes Biomolecular Condensate Function

Biomolecular condensates (BMCs) are dynamic membrane-free compartments that organize cellular biochemistry by concentrating selected molecules. However, the molecular parameters that govern both the formation and behavior of these condensates are not well understood. A recent study reveals that scaffold binding affinity (Kd) plays a crucial role in determining condensate phase behavior, internal dynamics, and biochemical output.

In a modular SUMO-SIM system, where scaffold valency was held constant while binding affinity was systematically varied, researchers found that affinity directly influences the phase boundary, resistance to chemical perturbation, and molecular mobility of condensates both in vitro and in human cells. In mixtures containing multiple components, the scaffold with the highest affinity dominated the dense-phase composition and dynamics, establishing a hierarchical rule for condensate organization.

Additionally, affinity-dependent changes in condensate dynamics result in tunable enzyme activity, demonstrating that binding energetics can be engineered to program condensate biochemistry.