Material properties of biomolecular condensates emerge from nanoscale dynamics

Biomolecular condensates form by phase separation of biological polymers. The cellular functions of such membraneless organelles are closely linked to their physical properties across length- and timescales: from the nanoscale dynamics of individual molecules, to the microscale translational diffusion within condensates, to their mesoscale viscoelasticity. However, the quantitative relationships between these characteristics have remained unclear. We addressed this question by combining single-molecule fluorescence, nanosecond correlation spectroscopy, microrheology, and large-scale molecular dynamics simulations, which we apply to a series of condensates formed by complex coacervation of highly charged disordered proteins spanning about two orders of magnitude in molecular dynamics, diffusivity, and viscosity. We find that the nanoscale chain dynamics of proteins in the dense phases occurs on timescales from ~100 ns to ~10 μs. Remarkably, the chain dynamics can be related quantitatively to both translational diffusion and mesoscale condensate viscosity by analytical relations from polymer physics. Atomistic simulations reveal that the differences in friction — a key quantity underlying these relations — are caused by differences in inter-residue contact lifetimes, thereby leading to the vastly different dynamics among the condensates. The rapid exchange of inter-residue contacts we observe may be a general mechanism for preventing dynamic arrest in compartments densely packed with polyelectrolytes, such as the cell nucleus.