Abstract

Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. Ample evidence now indicates biomolecular condensates as viscoelastic fluids, where shear stress relaxes at a finite rate, not instantaneously as in viscous liquids. Yet the fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the viscocapillary ratio (viscosity over interfacial tension). Here we used optically trapped polystyrene beads to measure the viscous and elastic moduli and the interfacial tensions of four types of droplets. Our results challenge the viscocapillary model, and reveal that the relaxation of shear stress governs fusion dynamics. These findings likely have implications for other dynamic processes such as multiphase organization, assembly and disassembly, and aging.

Highlights

  • Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging

  • In stress granules and many other cases, a dynamic, liquid state allows for rapid assembly, disassembly, or clearance in response to biochemical or environmental cues and for easy exchange of ligands or macromolecular components with the surrounding bulk phase[1,2,4,12,13,14]

  • Liquid droplets have a tendency to fuse and relax into a spherical shape, and the fusion speed has been used as an indicator of condensate dynamics[4,6,7,9,12,18,20,21,22,23,24,25,26,27]

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Summary

Introduction

Phase-separated biomolecular condensates must respond agilely to biochemical and environmental cues in performing their wide-ranging cellular functions, but our understanding of condensate dynamics is lagging. The fusion dynamics of condensate droplets has only been modeled based on viscous liquids, with fusion time given by the viscocapillary ratio (viscosity over interfacial tension). Our results challenge the viscocapillary model, and reveal that the relaxation of shear stress governs fusion dynamics. These findings likely have implications for other dynamic processes such as multiphase organization, assembly and disassembly, and aging. All fusion data have been analyzed by modeling condensates as purely viscous (i.e., Newtonian) liquids, where fusion, driven by interfacial tension (capillarity; γ) but retarded by viscosity (η), occurs on the viscocapillary timescale τvc 1⁄4 ηR=γ, where R denotes droplet radius. The four oppositely charged binary mixtures, pK:H, p:H, S:P, and S:L, form droplets, which fall under gravity, fuse, and settle on a coverslip with tallness sustained by interfacial tension (Fig. 1b)

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