title: Self-assembly of short aβ(16-22) peptides: effect of terminal capping and the role of electrostatic interaction.
abstract: We report the characterization of self-assembly of two short β-amyloid (Aβ) peptides (16-22), KLVFFAE and Ac-KLVFFAE-NH2, focusing on examining the effect of terminal capping. At pH 2.0, TEM and AFM imaging revealed that the uncapped peptide self-assembled into long, straight, and unbranched nanofibrils with a diameter of 3.8 ± 1.0 nm while the capped one formed nanotapes with a width of 70.0 ± 25.0 nm. CD analysis indicated the formation of β-sheet structures in both aggregated systems, but the characteristic CD peaks were less intense and less red-shifted for the uncapped than the capped one, indicative of weaker hydrogen bonding and weaker π-π stacking. Fluorescence and rheological measurements also confirmed stronger intermolecular attraction associated with the capped nanotapes. At acidic pH 2, each uncapped KLVFFAE molecule carries two positive charges at the N-terminus, and the strong electrostatic repulsion favors interfacial curving and twisting within the β-sheet, causing weakening of hydrogen bonds and π-π stacking. In contrast, capping reduces the charge by half, and intermolecular electrostatic repulsion is drastically reduced. As a result, the lateral attraction of β-sheets favors stronger lamellar structuring, leading to the formation of rather flat nanotapes. Flat tapes with similar morphological structure were also formed by the capped peptide at pH 12.0 where the charge on the capping end was reversed. This study has thus demonstrated how self-assembled nanostructures of small peptides can be manipulated through simple molecular structure design and tuning of electrostatic interaction.
authors.affiliation: Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266555, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Tao
authors.forename: Jiqian
authors.initials: J
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Chengdong
authors.initials: C
authors.lastname: Wang
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.forename: Xiubo
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
mesh_terms: D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010316:Particle Size; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22)