Disulfide-Rich Self-Assembling Peptides Based on Aromatic Amino Acid

Area of Science:

• Biomaterials Science
• Peptide Chemistry
• Supramolecular Chemistry

Background:

• Aromatic residues drive peptide self-assembly via π-π stacking and hydrophobic interactions.
• Systematic studies on the impact of individual aromatic amino acids in assembling peptides are limited.
• Aromatic capping groups have been explored, but the role of single amino acids needs further investigation.

Purpose of the Study:

• To systematically investigate the influence of aromatic-aromatic interactions on disulfide-rich assembling peptides.
• To evaluate the effects of incorporating three different aromatic amino acids on peptide folding, self-assembly, and rheology.
• To assess the biocompatibility and potential of resulting hydrogels for 3D cell culture.

Main Methods:

• Incorporation of three distinct aromatic amino acids into disulfide-rich assembling peptides.
• Evaluation of folding propensity, self-assembling properties (critical aggregation concentration), and rheological behaviors.
• Assessment of hydrogel biocompatibility using cell culture (SHED and NIH3T3 cells).

Main Results:

• Different aromatic-aromatic interactions significantly impact peptide self-assembly abilities, as shown by critical aggregation concentration (CAC) measurements.
• The injectable F1-ox hydrogel exhibits excellent biocompatibility with SHED and NIH3T3 cells.
• The hydrogel possesses a porous structure conducive to nutrient and waste exchange, supporting 3D cell culture.

Conclusions:

• Aromatic residues play a critical role in the molecular design of disulfide-rich assembling peptides.
• Tailoring aromatic-aromatic interactions offers a strategy for controlling peptide self-assembly and biomaterial properties.
• These findings provide insights for developing novel peptide-based biomaterials for biomedical applications, including 3D cell culture.