Decoding nucleic acid contributions to phase separation and ordering in biomolecular condensates.

Area of Science:

• Biophysics
• Molecular Biology
• Synthetic Biology

Background:

• Liquid-liquid phase separation (LLPS) is crucial for cellular organization, involving proteins and nucleic acids (NAs).
• While protein roles in LLPS are well-studied, NA contributions remain less explored.
• Understanding NA influence is key for both fundamental biology and synthetic applications.

Purpose of the Study:

• To investigate the impact of nucleic acid properties on LLPS.
• To develop a metric for assessing biocondensate stability.
• To characterize the emergence of liquid crystalline order within LLPS droplets.

Main Methods:

• Utilized model systems of oligonucleotides with controlled lengths and hybridization.
• Combined experimental techniques with molecular dynamics simulations.
• Analyzed phase behavior and dynamics across multiple length scales.

Main Results:

• Demonstrated distinct effects of NA properties on phase behavior.
• Proposed a novel metric for biocondensate stability.
• Identified conditions for liquid crystalline order, showing slowed NA dynamics and mobile peptides.

Conclusions:

• Oligonucleotide properties critically regulate LLPS and biocondensate characteristics.
• The findings provide a framework for designing synthetic NA-based coacervates.
• Results are generalizable to diverse natural and non-natural nucleic acid structures.