LASSI: A lattice model for simulating phase transitions of multivalent proteins

Area of Science:

• Biochemistry
• Computational Biology
• Biophysics

Background:

• Biomolecular condensates form through phase transitions driven by multivalent proteins with "stickers-and-spacers" architecture.
• These proteins utilize reversible crosslinks (stickers) and solvent interactions (spacers) to regulate phase behavior.

Purpose of the Study:

• To develop an open-source computational engine, LASSI, for calculating phase diagrams of multicomponent systems with multivalent proteins.
• To model spontaneous phase transitions and understand the structural organization of biomolecular condensates.

Main Methods:

• Development of the LASSI (LAttice simulation engine for Sticker and Spacer Interactions) computational engine.
• Coarse-grained simulations of multicomponent mixtures including linear and branched multivalent proteins and RNA molecules.

Main Results:

• Dense phases of condensates are characterized as droplet-spanning networks formed by reversible physical crosslinks.
• Condensate stoichiometry and dwell times correlate with internal structural organization (density and networking).
• Saturation concentration thresholds do not apply to multicomponent systems driven by heterotypic interactions, indicated by ellipsoidal phase diagrams.

Conclusions:

• LASSI enables efficient modeling of biomolecular condensate phase diagrams.
• Condensate structure is network-based, with internal organization influencing observable properties.
• Phase transition regulation in multicomponent systems differs from simple models, with implications for cellular processes.