Hollow condensates emerge from gelation-induced spinodal decomposition

Area of Science:

• Biochemistry
• Biophysics
• Molecular Biology

Background:

• Hollow biomolecular condensates feature depleted interiors and enriched shells.
• The general thermodynamic drivers for their formation are not fully understood.

Purpose of the Study:

• To investigate the mechanism behind hollow condensate formation using a p53 and dsDNA system.
• To elucidate the thermodynamic driving forces and morphological transitions involved.

Main Methods:

• Studied p53 and double-stranded DNA (dsDNA) interactions.
• Utilized in vitro assays to observe condensate morphology and material properties.
• Developed and employed a three-component phase-field model for simulations.

Main Results:

• Specific dsDNA with p53-binding motifs induced a transition to hollow, gel-like condensates.
• p21 DNA-induced peripheral gelation was identified as the key driver.
• Simulations confirmed peripheral gelation leads to core depletion, spinodal decomposition, and lumen formation.

Conclusions:

• Peripheral gelation is a key mechanism for forming multicomponent hollow condensates.
• This study provides mechanistic insights into the formation of complex intracellular structures.
• The findings contribute to understanding the thermodynamics and dynamics of biomolecular condensates.