Macromolecular Regulation of the Material Properties of Biomolecular Condensates.

Biomolecular condensates inside cells contain dozens to hundreds of macromolecular components and are surrounded by many others. Our computational studies predicted that macromolecular regulators have matching effects on the phase equilibrium and interfacial tension of condensates. Here we validate this prediction experimentally and characterize the effects of macromolecular regulators on other material properties, including viscoelasticity and fusion speed. Local melting due to the heating of a laser beam and turbidity assay both show that Ficoll70 raises the melting temperature of condensates formed by polylysine:heparin mixtures, whereas optical-tweezer measurements reveal parallel increases in interfacial tension. Additional optical-tweezer experiments report elevations in viscosity and shear relaxation time but also fusion speed by Ficoll70. The fusion speed is higher than predicted by modeling the condensates as purely viscous, demonstrating viscoelasticity and shear thinning. These results illustrate the ample opportunities for macromolecular regulators to tune material properties for proper functions of biomolecular condensates.