Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions

Area of Science:

• Cell biology
• Biophysics
• Biochemistry

Background:

• Membraneless organelles, or biomolecular condensates, are crucial for cellular compartmentalization.
• Attractive forces stabilizing condensates are known, but repulsive forces and their balance are less understood.

Purpose of the Study:

• To investigate the role of repulsive and attractive electrostatic interactions in regulating biomolecular condensate properties.
• To explore how signaling ions influence condensate stability and molecular partitioning.

Main Methods:

• In vitro and in-cell experiments using model proteins (Ddx3, Ddx4).
• Utilizing a polymerization model with generalized stickers and spacers.
• Analyzing effects of pH, salt concentration, and amino acid sequence variations.

Main Results:

• Electrostatic interactions (repulsive and attractive) dictate condensate stability, internal mobility, interfaces, and molecular partitioning.
• Signaling ions, such as calcium, directly bind to negatively charged amino acid sidechains, inverting their charge and altering repulsions.
• The polymerization model accurately predicts condensate stability across various conditions.

Conclusions:

• Electrostatic forces and their modulation by ions are critical regulators of biomolecular condensate behavior.
• A quantitative model is presented for understanding reversible control of condensate stability by charge and ions.