Hierarchical self-assembly of Tjernberg peptide at nanoscale

Abstract

Molecular self-assembly of biomolecules, especially proteins and peptides has elucidated much interest in recent years due to the reproducibility of structures and the high degree of control on the formation kinetics and morphology by varying the self-assembling conditions. These self-assembled structures have found widespread applications in tissue engineering, drug delivery and electronics. Two pentapeptides, namely Soto peptide (LPFFD) and the Tjernberg peptide (KLVFF), have been proposed to effectively curtail amyloid plaque deposits. Being amphipathic, these molecules can undergo self-assembly that can be influenced by a host of factors including concentration, pH, proteins, salt content, etc. However, this facet is scarcely explored till date, which might pave way for the novel treatment strategy for Alzheimer's disease. Our data show that the peptide spontaneously forms micelles and they are rich in beta sheet structures, which is confirmed using FT-IR, SAED and thioflavin binding studies. While, acidic pH seems to have no role in the formation of higher order structures, alkaline pH promotes longitudinal and lateral stacking interactions resulting in formation of higher order structures. We also found that the hydrophobicity and hydrophilicity of the substrate also play a major role in the formation of higher order structures. Moreover, the micelles formed by the KLVFF peptide under various environmental conditions exhibits excellent surface tension lowering effects which is in good agreement with the cell proliferation data that showed the protective ability of KLVFF peptide against Aβ1–42 cytotoxicity indicating its potential in Alzheimer's disease therapy as an aggregation blocking agent.