Self-assembly of short aβ(16-22) peptides: effect of terminal capping and the role of electrostatic interaction

Langmuir. 2011 Mar 15;27(6):2723-30. doi: 10.1021/la1034273. Epub 2011 Feb 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / chemical synthesis*
  • Amyloid beta-Peptides / chemistry
  • Particle Size
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / chemistry
  • Static Electricity
  • Surface Properties

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (16-22)