Hydrophobicity regulates self-assembly behavior of binding-induced fibrillogenesis peptides

Binding-induced fibrillogenesis (BIF) peptides have a promising future in biomedicine due to the processiblity in situ in vivo, which bind to a specific trigger and in situ self-assemble into nanofibrous structures (BIF process) with excellent physical/biological functions. Alkyl chains in BIF peptides as hydrophobic tails have an important effect on self-assembly behaviors of BIF peptides. Herein, BIF peptides (trigger: Ca2+ or integrin) with different hydrophobic alkyl chains are designed to explore the influence of hydrophobicity on self-assembly behaviors of BIF peptides (Abbreviation as BIF4, BIF8, and BIF16 for 4, 8, 16 carbons of alkyl chains). It is found that BIF peptides with weak hydrophobicity (BIF4) do not form fibrous structure upon binding to Ca2+, but in nanoparticle formulation. While with strong hydrophobicity, BIF16 initially self-assemble into nanoparticles, which further bind to Ca2+ and self-assemble into nanofibers with a β-sheet conformation. As a result, when incubated with HUVECs overexpressing integrins on surfaces, BIF4 were internalized as nanoparticles without BIF process, but BIF16 performed BIF process and attached on cell surfaces. This study provides experimental evidences of the hydrophobicity effect on self-assembly behavior of BIF peptides and directs applications of BIF peptides with controllable self-assembly