Amyloid‐like aggregation of designer bolaamphiphilic peptides: Effect of hydrophobic section and hydrophilic heads

Abstract

Amyloid-like aggregation of natural proteins or polypeptides is an important process involved in many human diseases as well as some normal biological functions. Plenty of works have been done on this ubiquitous phenomenon, but the molecular mechanism of amyloid-like aggregation has not been fully understood yet. In this study, we showed that a series of designer bolaamphiphilic peptides could undergo amyloid-like aggregation even though they didn't possess typical β-sheet secondary structure. Through systematic amino acid substitution, we found that for the self-assembling ability, the number and species of amino acid in hydrophobic section could be variable as long as enough hydrophobic interaction is provided, while different polar amino acids as the hydrophilic heads could change the self-assembling nanostructures with their aggregating behaviors affected by pH value change. Based on these results, novel self-assembling models and aggregating mechanisms were proposed, which might provide new insight into the molecular basis of amyloid-like aggregation.

Self-Assembling Peptides and Their Application in the Treatment of Diseases

“…For example, K and R in KAAAAK (KA4K), KAAAAAAK (KA6K), and RAAAAAAR (RA6R) bolaamphiphilic peptides have hydrophilic character and are connected by the hydrophobic A residues. Their assembled product has a fibrous form [26]. Another bolaamphiphilic peptide, EFLLLLFE (EFL4FE), which contains an E residue, shows a flat membrane extension and forms peptide nanotubes by concentration differences [28].…”

“…Another bolaamphiphilic peptide, EFLLLLFE (EFL4FE), which contains an E residue, shows a flat membrane extension and forms peptide nanotubes by concentration differences [28]. As the charge of amino acids is altered in different pH conditions, based on their molecular properties, these bolaamphiphilic peptides may aggregate or disaggregate according to the environmental pH [26]. Bolaamphiphiles are a category of emerging nanomaterials with the ability to self-assemble into various valuable nanostructures [49,50,51].…”

Amphiphilic peptides as novel nanomaterials: design, self-assembly and application

“…Although systematic study on this issue is rare, it has been proved that solution parameters such as pH value and solvent property have critical effects on self-assembling behaviors of amphiphilic peptides. 85,86 Since it has been discussed earlier that charges in hydrophilic heads are very important for self-assembly, and the net charge of a hydrophilic amino acid is determined by the environmental pH value, it is clear that the pH value of a solution will affect the self-assembling behaviors by affecting the charges. In fact, nearly all self-assembling amphiphilic peptides have been investigated in a limited range of pH, only within which the peptide molecules could undergo self-assembly as expected.…”

Controllable self-patterning behaviours of flexible self-assembling peptide nanofibers

“…In our previous studies, we have proved that the selfassembling process of peptide monomers could be rationally controlled by deliberate peptide design, such as changing the charge distribution and geometrical shape of peptides [19][20][21] . On the other hand, environmental parameters such as pH and solvent polarity could also affect the morphology of nanostructures and their alignment 21,22 . These findings suggested that by deliberate peptide design and environment control, it's possible to fabricate desired nanostructures with controllable patterning behaviour.…”