Submicron polymeric particles accelerate insulin fibrillation by surface adsorption.

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Insulin fibrillation forms insoluble aggregates from unfolded proteins.
• Engineered nanoparticles are known to influence protein fibrillation kinetics.
• The precise mechanisms of particle-mediated insulin fibrillation remain unclear.

Purpose of the Study:

• To investigate how surface-modified polystyrene nanoparticles affect insulin fibrillation.
• To elucidate the role of particle surface properties and concentration in protein aggregation.
• To understand the underlying mechanisms of particle-enhanced protein fibrillation.

Main Methods:

• Experimental investigation of insulin fibrillation with amine- and sulfate-modified polystyrene nanoparticles (200 nm).
• Quantification of fibrillation rates using thioflavin T fluorescence.
• Analysis of protein adsorption onto particle surfaces.
• Monte Carlo simulations to model protein fibrillation on surfaces.

Main Results:

• Both particle types enhanced insulin fibrillation rates at high concentrations (1:1 protein to particle mass ratio).
• Significant protein adsorption occurred on particle surfaces, indicating nucleation.
• Particle presence did not significantly alter the secondary structure change (α-helix to β-sheet) during fibrillation.
• Simulations confirmed that increased protein-surface affinity enhances fibrillation by increasing local concentration and stabilizing intermediates.

Conclusions:

• Engineered nanoparticles, particularly at high concentrations, can act as nucleation sites promoting insulin fibrillation.
• Increased protein-surface affinity is a key factor in particle-induced acceleration of fibrillation.
• Findings offer insights into particle-protein interactions, relevant for nanotoxicity and biomaterial design.