Nonionic peptide amphiphiles and their supramolecular co-assemblies tune charge density and bioactivity

Area of Science:

• Biomaterials Science
• Supramolecular Chemistry
• Nanotechnology

Background:

• Supramolecular peptide assemblies often require ionic groups for solubility, but charge can negatively impact biological functions.
• Cationic residues can cause cell toxicity, and charged amino acids result in structures sensitive to pH and ionic strength.

Purpose of the Study:

• To synthesize nonionic peptide amphiphiles (PAs) with decaethylene glycol segments.
• To explore supramolecular co-assembly of nonionic and ionic PAs to create uncharged assemblies with tunable charge density.
• To investigate the impact of nonionic PAs and co-assemblies on the bioactivity of supramolecular nanostructures.

Main Methods:

• Synthesis of nonionic peptide amphiphiles (PAs) incorporating a decaethylene glycol segment.
• Supramolecular co-assembly of nonionic PAs with charged PA monomers.
• Characterization of self-assembly behavior, morphology, and internal structure (β-sheets).
• In vitro assessment of osteogenic differentiation of mesenchymal stem cells using different PA assemblies.

Main Results:

• Nonionic PAs self-assemble into high-aspect ratio filaments with β-sheets, stable across various pH and ionic conditions.
• Co-assembly of nonionic and ionic PAs yields supramolecular copolymers with tunable surface charge density and enhanced internal order.
• Assemblies with nonionic PAs or co-assemblies showed greater bioactivity in an osteogenic differentiation model compared to fully charged assemblies.

Conclusions:

• Nonionic PAs and their co-assemblies offer a strategy to create stable, uncharged supramolecular nanostructures.
• Tunable charge density in co-assemblies enhances bioactivity, potentially through synergistic protein binding and increased supramolecular dynamics.
• These findings provide a platform for investigating the role of charge density in the bioactivity of water-soluble supramolecular nanostructures.