Biomolecular condensates form spatially inhomogeneous network fluids

Area of Science:

• Cell Biology
• Biophysics
• Structural Biology

Background:

• Biomolecular condensates are crucial for cellular functions, with their properties influenced by internal molecular organization.
• Structural characterization of these condensates is challenging, limiting our understanding of their material properties.

Purpose of the Study:

• To structurally characterize model condensates formed by macromolecules from nucleolar granular components (GCs).
• To elucidate the relationship between internal organization, material properties, and molecular dynamics within these condensates.

Main Methods:

• Utilized a combination of small-angle neutron scattering (SANS) and fluorescence recovery after photobleaching (FRAP).
• Employed coarse-grained molecular dynamics (MD) simulations for detailed structural descriptions.
• Focused on minimal facsimiles of nucleolar granular components (GCs).

Main Results:

• GC-mimicking macromolecules form network fluids with spatial inhomogeneities across multiple length scales.
• These inhomogeneities arise from distinct protein and peptide domain contributions.
• A coexistence of liquid- and gas-like macromolecular densities was observed, leading to bimodal internal molecular dynamics.

Conclusions:

• The network-fluid organization of these condensates dictates their material properties and dynamics.
• Insights suggest that condensates formed by multivalent proteins share characteristics with colloidal systems like patchy or hairy colloids.
• This study provides a structural basis for understanding condensate function and behavior.