Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent...

Area of Science:

• Biophysics
• Cell Biology
• Polymer Physics

Background:

• Intracellular membraneless bodies form via phase transitions of linear multivalent proteins.
• These proteins form system-spanning networks (gels) through non-covalent crosslinks.
• Gelation can occur with or without phase separation, with the latter being biologically preferred.

Purpose of the Study:

• To investigate the physical properties of intrinsically disordered linkers.
• To determine how these properties influence the gelation of multivalent proteins.
• To understand the role of linkers in driving phase separation during gelation.

Main Methods:

• Coarse-grained computer simulations.
• Application of associative polymer theory.
• Analysis of protein linker sequences and their impact on phase transitions.

Main Results:

• Identified specific physical properties of disordered linkers that dictate the extent of phase separation-driven gelation.
• Demonstrated that gelation driven by phase separation occurs at lower protein concentrations.
• Showed that sequence-encoded information in disordered linkers is crucial for controlling phase transitions.

Conclusions:

• Intrinsically disordered linkers play a critical role in modulating phase transitions of multivalent proteins.
• Understanding linker properties is key to deciphering the formation mechanisms of membraneless organelles.
• This research provides insights into how protein sequence dictates biological function through physical principles.