Biomolecular condensate microstructure is invariant to sequence-encoded molecular and macroscopic properties
Year: 2025
Type: article
Abstract: short pathlengths. However, a framework linking single-molecule properties, condensate microstructure, and macroscopic material properties remains elusive. Here, we combine molecular simulation and graph-theoretic analysis to reveal that small-world microstructures are inherent properties of LCD-like polymers, whose sequence features impact both molecule-scale conformations and droplet-scale material properties while maintaining a stable network structure. Using a residue-resolution coarse-grained model, we probe condensates comprising naturally-occuring LCD sequences and generalize our findings by varying composition and patterning in binary sequences of hydrophobic and polar residues. We show that non-blocky sequences, including a hydrophobic homopolymer, form condensates with small-world internal networks featuring "hubs"-molecules responsible for global connectivity-and "cliques", molecular clusters bound by persistent short-ranged associations. Cliques localize near interfaces without a secondary phase transition, suggesting a role in mediating molecular partitioning and condensate aging by tuning interfacial material properties. Moreover, we discover that network small-worldness and droplet surface tension are consequences of sequence length and hydrophobicity. We also track single-molecule structure and dynamics inside condensates, revealing that internal heterogeneity at the single-molecule level is systematically encoded by network topology. Collectively, our work establishes multiscale structure-property relationships in LCD condensates, elucidating general organizing principles of the condensate microstructure that persist with sequence-driven changes in molecular behaviors and material properties.
Source: Soft Matter
DOI: 10.1039/d5sm00740b
Authors: Daniel Tan, Dilimulati Aierken, Pablo L. Garcia, Jerelle A. Joseph
Institution: Princeton University
Language: English
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
OpenAlex ID: W4414440887