Insulin fibril inhibition using glycopolymeric nanoassemblies

Area of Science:

• Biochemistry
• Polymer Chemistry
• Materials Science

Background:

• Insulin protein misfolding and aggregation into amyloid plaques are implicated in various diseases.
• Current therapeutic strategies face challenges in addressing protein homeostasis disruptions.

Purpose of the Study:

• To synthesize and characterize novel glycopolymeric nanoassemblies for inhibiting insulin fibrillation.
• To investigate the mechanisms underlying the inhibition of insulin amyloid formation by these nanoassemblies.

Main Methods:

• Synthesis of block copolymers using reversible addition-fragmentation chain transfer (RAFT) polymerization.
• Characterization of self-assembled nanoaggregates using critical aggregation concentration (CAC), dynamic light scattering (DLS), and transmission electron microscopy (TEM).
• Assessment of insulin fibrillation inhibition using biophysical techniques including fluorescence spectroscopy (Tyrosine, Nile Red, temperature-dependent) and isothermal titration calorimetry (ITC), complemented by molecular dynamics simulations.

Main Results:

• Amphiphilic glycopolymeric nanoassemblies were successfully synthesized and characterized.
• These nanoassemblies demonstrated significant inhibition of insulin fibrillation.
• Hydrophobic, electrostatic, and hydrogen bonding interactions were identified as key mechanisms mediating the inhibition of insulin aggregation.

Conclusions:

• Novel glycopolymeric nanoassemblies are effective inhibitors of insulin fibrillation.
• The study elucidates the multi-modal interaction mechanisms between the nanoassemblies and insulin aggregates.
• These findings offer potential therapeutic avenues for diseases associated with protein misfolding and amyloid formation.