Nanoscale profiling of evolving intermolecular interactions in ageing FUS condensates

Area of Science:

• Biochemistry
• Cell Biology
• Materials Science

Background:

• Protein condensates exhibit distinct material properties crucial for cellular functions.
• Characterizing these properties is challenging due to technical limitations in studying condensed states.

Purpose of the Study:

• To develop and apply a novel technology platform for characterizing the time-dependent material properties of protein condensates.
• To investigate the phase transitions and molecular conformations within FUS (fused in sarcoma) protein condensates.

Main Methods:

• Combined microfluidic sample deposition to preserve condensate properties with nanometre-resolution spatial mapping.
• Utilized the FUS protein to study condensate material properties and phase transitions.

Main Results:

• Observed two distinct phase transitions within FUS condensates.
• Identified a disorder-to-order transition at condensate interfaces linked to β-sheet formation.
• Documented core gelation driven by increased interactions within intrinsically disordered regions.

Conclusions:

• Established a technology platform for studying nanometre-scale phase changes in protein condensates.
• Identified specific molecular conformations associated with emergent phases in FUS condensates.
• Provides insights into the role of material property dynamics in condensate function.