Structural Consequences of Introducing Bioactive Domains to Designer β-Sheet Peptide Self-Assemblies

Area of Science:

• Biomaterials Science
• Molecular Biology
• Nanotechnology

Background:

• Multidomain peptides combine self-assembling β-sheet domains for nanoscale properties with bioactive domains for specific biological responses.
• Previous research established the efficacy of these peptides, but lacked molecular-level structural characterization.
• The intended design requires bioactive domains to remain solvent-accessible, separate from the β-sheet structure.

Purpose of the Study:

• To investigate the structural consequences of incorporating bioactive domains into self-assembling β-sheet peptides.
• To evaluate potential outcomes: no effect, incorporation into the β-sheet, or interference with self-assembly.
• To provide molecular-level insights into the design of bioactive peptide hydrogels.

Main Methods:

• Solid- and solution-state nuclear magnetic resonance (NMR) spectroscopy were employed.
• Peptides incorporated self-assembling (SL)6 motifs and various bioactive domains (VEGF-A mimic, IGF-1 mimic, SARS-CoV-2 binding peptide).
• Structural analysis focused on the interaction between bioactive and self-assembling domains.

Main Results:

• Observed all three anticipated structural outcomes: no effect, β-sheet incorporation, and self-assembly interference.
• Demonstrated that bioactive domains can have unintended structural consequences.
• Highlighted the variability in structural outcomes depending on the specific peptide sequences.

Conclusions:

• The incorporation of bioactive domains into self-assembling peptides can lead to unpredictable structural changes.
• These structural alterations can adversely affect the intended biofunctionality and biomaterial properties of peptide hydrogels.
• Further research is needed to address challenges in designing highly tunable bioactive self-assembling peptide hydrogels.