Biomolecular condensates undergo a generic shear-mediated liquid-to-solid transition.

Area of Science:

• Biophysics
• Materials Science
• Cell Biology

Background:

• Membrane-less organelles, formed by liquid-liquid phase separation, regulate vital cellular functions.
• Protein condensates can transition from liquid to solid states, a process linked to neurodegenerative diseases.
• Silk spinning exemplifies a functional liquid-to-solid transition in protein condensates driven by shear.

Purpose of the Study:

• To investigate the factors controlling pathological gelation in functional protein condensates.
• To explore the propensity of protein and peptide systems to undergo liquid-to-solid transitions under mechanical shear.
• To understand the role of shear stress in protein condensate gelation and fiber formation.

Main Methods:

• Utilized microfluidics to precisely control mechanical shear application on protein condensates.
• Generated single-protein fibers from liquid-liquid phase separated condensates.
• Characterized the structural and material properties of the generated fibers as a function of shear stress.

Main Results:

• Four proteins and one peptide system exhibited a strong propensity for liquid-to-solid transition upon exposure to low mechanical shear.
• Fiber formation from single-protein condensates was achieved using controlled shear.
• Generic backbone-backbone hydrogen bonding constraints were identified as key determinants of the liquid-to-solid transition.

Conclusions:

• Mechanical shear is a significant factor in the irreversible liquid-to-solid transition of protein condensates.
• Physical factors, particularly shear, play a crucial role in protein aggregation relevant to diseases.
• These findings open avenues for developing artificial shear-responsive biomaterials.