High-Resolution Insights into the Stepwise Self-Assembly of Nanofiber from Bioactive Peptides

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Peptide self-assembly is crucial for biological function, improving peptide bioactivity and lifespan.
• Understanding self-assembly mechanisms is key to designing advanced bioactive peptides.

Purpose of the Study:

• To investigate the self-assembly mechanism of the therapeutic peptide PTP-7S.
• To elucidate the driving forces and structural transitions during PTP-7S self-assembly.
• To explore the potential of self-assembled PTP-7S for clinical applications.

Main Methods:

• Atomic Force Microscopy (AFM) for structural visualization.
• Circular Dichroism (CD) spectroscopy for secondary structure determination.
• 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence for conformational changes.
• Coarse-grained (CG) dynamic simulations for mechanistic insights.

Main Results:

• PTP-7S adopts an α-helical structure and self-assembles into nanofibers.
• Self-assembly occurs stepwise: monomers form charged peptide-assembling units (PUs), which then aggregate into nanofibers.
• Hydrophobic forces drive PU formation, while electrostatic interactions mediate nanofiber assembly and growth.
• A sequence principle for self-assembly involves balancing counter charges and hydrophobicity.

Conclusions:

• The study reveals the molecular mechanism of PTP-7S self-assembly.
• Self-assembled PTP-7S exhibits enhanced anticancer activity, protease resistance, and sustained drug release.
• Findings provide a foundation for developing innovative self-assembled bioactive peptides for therapeutic use.