Differences in cytotoxicity of β-sheet peptides originated from silk and amyloid β

Macromol Biosci. 2011 Jan 10;11(1):60-4. doi: 10.1002/mabi.201000250. Epub 2010 Oct 15.

Abstract

The relationships between amino acid sequence, nano-assemblies, and cytotoxicity to neuron cytotoxicity were investigated using β-sheet-forming peptides from Araneus ventricosus spider silk, and amyloid forming peptides Aβ(12-28) (β1), Aβ(28-42) (β2), and full-length Aβ(1-42). Although silk derived peptides formed nano-assemblies, nanofilaments, and nanofibrils with β-sheet contents raging from 24 to 40%, they showed no significant cytotoxicity to neurons. In contrast, nano-assemblies and nanofibrils formed from Aβ peptides with high β-sheet content demonstrated cytotoxicity to the neurons. These differences in cell response between the silk β-sheets and Aβ peptides indicate that the general propensity to form beta sheets and form nanostructures is not sufficient to predict cytotoxicity, while surface charges of the assemblies are significant factors that impact cytotoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Cell Survival / drug effects*
  • Fibroins / chemistry
  • Fibroins / toxicity*
  • Humans
  • Nanofibers
  • PC12 Cells
  • Protein Structure, Secondary
  • Rats
  • Spiders
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Fibroins