Biomolecular condensate microstructure is invariant to sequence-encoded molecular and macroscopic properties

Area of Science:

• Biophysics
• Soft Matter Physics
• Computational Biology

Background:

• Biomolecular condensates, including those from prion-like low complexity domains (LCDs), are crucial for cellular function.
• These condensates are regulated by complex molecular interaction networks.
• Previous studies suggested distinct conformations and predicted small-world network microstructures in LCD condensates.

Purpose of the Study:

• To establish a framework linking single-molecule properties, condensate microstructure, and macroscopic material properties.
• To investigate the inherent small-world network properties of LCD-like polymers.
• To elucidate the general organizing principles of condensate microstructure.

Main Methods:

• Molecular simulation using a residue-resolution coarse-grained model.
• Graph-theoretic analysis of condensate microstructures.
• Investigation of naturally occurring and designed binary LCD sequences.

Main Results:

• LCD condensates inherently form small-world networks with hubs and cliques.
• Sequence features, such as non-blocky patterns and hydrophobicity, influence network topology and material properties like surface tension.
• Internal heterogeneity at the single-molecule level is encoded by network topology.

Conclusions:

• Small-world microstructures are a fundamental property of LCD condensates.
• Sequence composition and patterning systematically control multiscale structure-property relationships.
• This work provides general principles for understanding condensate organization and function.