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: Ca 2+ or integrin) with different hydrophobic alkyl chains are designed to explore the influence of hydrophobicity on self-assembly behaviors of BIF peptides (Abbreviation as BIF 4 , BIF 8 , and BIF 16 for 4, 8, 16 carbons of alkyl chains). It is found that BIF peptides with weak hydrophobicity (BIF 4 ) do not form fibrous structure upon binding to Ca 2+ , but in nanoparticle formulation. While with strong hydrophobicity, BIF 16 initially self-assemble into nanoparticles, which further bind to Ca 2+ and self-assemble into nanofibers with a β-sheet conformation. As a result, when incubated with HUVECs overexpressing integrins on surfaces, BIF 4 were internalized as nanoparticles without BIF process, but BIF 16 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