Biomolecular condensate microstructure couples molecular and mesoscale properties

Area of Science:

• Biophysics
• Molecular Biology
• Soft Matter Physics

Background:

• Biomolecular condensates are crucial cellular structures regulated by molecular interaction networks.
• Prion-like low complexity domains (LCDs) are key protein components forming these condensates.
• Previous studies predicted small-world network topologies and spatial inhomogeneities within single-component LCD condensates.

Purpose of the Study:

• To systematically characterize the molecular networks underlying biomolecular condensates.
• To investigate the relationship between single molecule properties and the resulting network topologies.
• To understand how network structure influences condensate organization and material properties.

Main Methods:

• Utilized a chemically specific coarse-grained model to simulate LCD condensates.
• Employed a generic hydrophobic-polar (HP) polymer model to generalize findings by varying sequence hydrophobicity.
• Analyzed network topologies, identifying molecular hubs and cliques using betweenness centrality.

Main Results:

• Condensates are sustained by small-world networks characterized by molecular hubs and cliques.
• Hubs, with high betweenness centrality, are elongated and located centrally; cliques are near the interface.
• Power-law relationships link single-molecule properties (structure, dynamics) to network betweenness centrality.

Conclusions:

• Condensate network connectivity inhomogeneities are predictable from individual molecule properties.
• Network cliques exhibit longer lifetimes and constrained molecular dynamics, suggesting a role in interface properties.
• This work provides a framework for understanding condensate formation and function through network principles.