Self-crowding induced phase separation in protein dispersions.

Area of Science:

• Theoretical biophysics
• Protein conformational dynamics
• Solution behavior modeling

Background:

• Protein folding and conformational changes are critical to biological function.
• Understanding how molecular volume and interactions affect protein behavior in solution is complex.
• Existing models often simplify the interplay between protein shape, volume, and phase behavior.

Purpose of the Study:

• To theoretically investigate the coupling between protein conformation, molecular volume, and solution phase behavior.
• To model a two-state protein system with reversible transitions between native and non-native states.
• To explore how varying particle volumes and attractive interactions influence protein stability and phase diagrams.

Main Methods:

• Development of a coarse-grained protein model representing conformers as spheres with distinct hard-core diameters.
• Theoretical analysis of protein behavior across different concentrations and interaction potentials.
• Calculation of a phase diagram to delineate regions of native and non-native state prevalence.

Main Results:

• The native protein state is stabilized by energetic factors at low concentrations.
• At high concentrations, the native state is stabilized by self-crowding (excluded volume effects).
• Attractive interactions between non-native proteins drive transitions, leading to a prevalent non-native state in intermediate regimes. The phase diagram is sensitive to volume differences and can lose its critical point.

Conclusions:

• Protein solution behavior is intricately linked to conformational state and molecular volume.
• Both energetic stabilization and excluded volume effects play crucial roles in protein conformational preferences.
• The model highlights the significant impact of subtle volume differences on protein phase behavior and stability.