Self-Assembled Peptide Nanofibrils Designed to Release Membrane-Lysing Antimicrobial Peptides

Area of Science:

• Biomaterials Science
• Antimicrobial Peptides
• Nanotechnology

Background:

• Antimicrobial peptides (AMPs) show promise against multidrug-resistant bacteria but suffer from poor in vivo stability and short-term activity.
• Self-assembled peptide materials can enhance AMP stability, but biosafety concerns, including potential protein misfolding and amyloid formation, exist.

Purpose of the Study:

• To design and construct self-assembled peptide-based nanofibrils for enhanced antimicrobial activity and stability.
• To evaluate the biosafety and biocompatibility of the developed peptide nanofibrils.

Main Methods:

• Design of two specific peptides.
• Self-assembly of peptides into nanofibrils.
• Assessment of nanofibril disassembly and peptide release in the presence of bacteria.
• Evaluation of antimicrobial activity, including bacterial membrane disruption and calcium efflux.
• Characterization of cytotoxicity, hemolytic activity, and biocompatibility of hybrid macrofilms.

Main Results:

• The peptide-based nanofibrils successfully released antimicrobial peptides through disassembly.
• The nanofibrils demonstrated potent, long-term antimicrobial activity by disrupting bacterial membranes and causing calcium efflux.
• Hybrid macrofilms constructed from these nanofibrils exhibited low cytotoxicity, low hemolytic activity, and good biocompatibility.

Conclusions:

• Self-assembled peptide nanofibrils offer a promising strategy to overcome the limitations of traditional antimicrobial peptides.
• This innovative design approach facilitates the development of stable, effective, and biocompatible antimicrobial nanomaterials.
• The developed peptide nanofibrils hold potential for combating multidrug-resistant bacterial infections.