Alternative Causal Link between Peptide Fibrillization and β-Strand Conformation

Abstract

In the prevailing phenomenon of peptide fibrillization, β-strand conformation has long been believed to be an important structural basis for peptide assembly. According to a widely accepted theory, in most peptide fibrillization processes, peptide monomers need to intrinsically take or transform to β-strand conformation before they can undergo ordered packing to form nanofibers. In this study, we reported our findings on an alternative peptide fibrillization pathway starting from a disordered secondary structure, which could then transform to β-strand after fibrillization. By using circular dichroism, thioflavin-T binding test, and transmission electron microscopy, we studied the secondary structure and assembly behavior of Ac-RADARADARADARADA-NH 2 (RADA16-I) in a low concentration range. The effects of peptide concentration, solvent polarity, pH, and temperature were investigated in detail. Our results showed that at very low concentrations, even though the peptide was in a disordered secondary structure, it could still form nanofibers through intermolecular assembly, and under higher peptide concentrations, the transformation from the disordered structure to β-strand could happen with the growth of nanofibers. Our results indicated that even without ordered β-strand conformation, driving forces such as hydrophobic interaction and electrostatic interaction could still play a determinative role in the self-assembly of peptides. At least in some cases, the formation of β-strand might be the consequence rather than the cause of peptide fibrillization.

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example

“…However, not all functionalized RADA16-I achieved good results. Numerous active motifs were covalently bound to RADA16-I, and the result showed that some functionalized RADA16-I showed no activity [ 55 ]. It is believed that the biological function of functionalized scaffolds depends not only on the biological activity of functional motifs but also on the presentation forms of functional motifs, such as mobility, conformation, and orientation.…”

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-Ⅰ as an Example

“…However, not all functionalized RADA16-Ⅰ achieved good results. Numerous active motifs were covalently bound to RADA16-Ⅰ, and the result showed that some functionalized RADA16-Ⅰ showed no activity [56]. It is believed that the biological function of functionalized scaffolds depends not only on the biological activity of functional motifs but also on the presentation forms of functional motifs such as mobility, conformation, and orientation.…”