Extreme dynamics in a biomolecular condensate.

Area of Science:

• Biochemistry
• Biophysics
• Cell Biology

Background:

• Proteins and nucleic acids phase-separate to form biomolecular condensates.
• Condensates organize cellular processes across molecular and mesoscopic scales.
• Understanding condensate dynamics at the molecular level is crucial but challenging.

Purpose of the Study:

• To investigate the molecular-scale dynamics within phase-separated biomolecular condensates.
• To explore the relationship between macroscopic viscosity and molecular mobility in these systems.
• To elucidate the mechanisms underlying rapid molecular rearrangements in concentrated protein phases.

Main Methods:

• Studied complex coacervates of oppositely charged disordered proteins.
• Utilized single-molecule spectroscopy optimized for droplet measurements.
• Performed all-atom molecular dynamics simulations.

Main Results:

• Phase-separated protein condensates exhibit 1000-fold concentration and 300-fold higher viscosity than water.
• Single-molecule spectroscopy revealed submicrosecond timescale interconversion of protein chain configurations.
• Molecular dynamics simulations confirmed pico- to nanosecond timescale exchange of charged side-chain interactions.

Conclusions:

• Despite high macroscopic viscosity, disordered proteins in condensates maintain high molecular mobility.
• Short-lived interactions between charged side chains drive rapid local rearrangements.
• Efficient molecular-scale reactions can occur within phase-separated biomolecular systems.