pH-Dependent Packing Mode Variations and Chirality Inversion in Short Peptide Self-Assembly.

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Chemical Biology

Background:

• Controlling peptide self-assembly structures and morphologies is a significant challenge.
• Amphiphilic peptides offer tunable self-assembly properties.
• Understanding chirality in self-assembled peptide systems is crucial for advanced materials.

Purpose of the Study:

• To investigate the pH-dependent self-assembly and chirality inversion of designed amphiphilic peptides.
• To elucidate the molecular mechanisms underlying pH-induced helix inversion in peptide nanofibrils.
• To explore strategies for engineering hierarchical chirality in peptide assemblies.

Main Methods:

• Design and synthesis of amphiphilic peptides (I3H).
• Characterization using microscopy, neutron scattering, and spectroscopy.
• Mechanistic studies involving pH titration, NMR, and molecular dynamics simulations.

Main Results:

• Peptides self-assemble into beta-sheet nanofibrils with pH-dependent helix handedness inversion.
• Histidine protonation state dictates antiparallel (low pH) vs. parallel (high pH) beta-sheet packing.
• Pi-pi stacking of deprotonated histidine drives chiral flipping and supramolecular helix inversion.
• Glycine insertion at the interface modulates the pH-dependent inversion effect.

Conclusions:

• The study reveals a mechanism for pH-dependent chirality inversion in peptide self-assembly driven by histidine interactions.
• Precise control over molecular packing and side-chain interactions enables the design of hierarchical chirality.
• This work provides a blueprint for designing functional peptide-based nanomaterials with tunable chiral properties.