Computer Simulations Show That Liquid-Liquid Phase Separation Enhances Self-Assembly

Area of Science:

• Biophysics
• Molecular Biology
• Computational Biology

Background:

• Biomolecular condensates, formed via liquid-liquid phase separation, are crucial for cellular functions and pathogen replication.
• Viruses utilize condensates for compartmentalizing capsid assembly and genome packaging within host cells.
• The physical principles governing condensate-mediated self-assembly are not fully understood.

Purpose of the Study:

• To investigate the impact of biomolecular condensates on the self-assembly of icosahedral capsids.
• To explore the physical principles controlling condensate-mediated assembly using computational models.
• To determine how condensates influence assembly efficiency and robustness.

Main Methods:

• Coarse-grained molecular dynamics simulations were employed.
• Capsid subunits were modeled using shape-based representations.
• Condensates were modeled implicitly to isolate phase separation effects.

Main Results:

• Condensates significantly enhance self-assembly rates, yields, and robustness.
• Excluded volume effects within condensates allow control over the number of assembled capsids.
• Aberrant, long-lived assembly intermediates were identified as a factor that can suppress yields.

Conclusions:

• Biomolecular condensates can effectively promote and regulate biological self-assembly processes.
• Computational modeling provides insights into controlling self-assembly via phase separation.
• Findings may inform the engineering of self-assembly systems using condensates.