Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity

Emerson R. Silva*, Eduardo Listik, Sang W. Han, Wendel A. Alves, Bruna M. Soares, Mehedi Reza, Janne Ruokolainen, Ian W. Hamley

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

We present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form [RF]n (n = 1–5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of [RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-β structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of [RF]n peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self-assemblies rich in cationic groups when interacting with cell membranes.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalBiophysical Chemistry
Volume233
DOIs
Publication statusPublished - 1 Feb 2018
MoE publication typeA1 Journal article-refereed

Keywords

  • Cross-β structure
  • Cytotoxicity
  • Fiber diffraction
  • Fibrillization
  • Scattering

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    Silva, E. R., Listik, E., Han, S. W., Alves, W. A., Soares, B. M., Reza, M., ... Hamley, I. W. (2018). Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity. Biophysical Chemistry, 233, 1-12. https://doi.org/10.1016/j.bpc.2017.11.005