Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides

Mello, L. R., Aguiar, R. B., Yamada, R. Y., Moraes, J. Z., Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926, Alves, W. A., Reza, M., Ruokolainen, J. and Silva, E. R. (2020) Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides. Journal of Materials Chemistry B, 8 (12). pp. 2495-2507. ISSN 0959-9428 doi: 10.1039/c9tb02219h

Abstract/Summary

Amphiphilicity is the most critical parameter in the self-assembly of surfactant-like peptides (SLPs), regulating the way by which hydrophobic attraction holds peptides together. Its effects go beyond supramolecular assembly and may also trigger different cell responses of bioactive peptide-based nanostructures. Herein, we investigate the self-assembly and cellular effects of nanostructures based on isomeric SLPs composed by arginine (R) and phenylalanine (F). Two amphipathic designs were studied: a diblock construct F4R4 and its bolaamphiphile analog R2F4R2. A strong sequence-dependent polymorphism emerges with appearance of globules and vesicle-like assemblies, or flat nanotapes and cylindrical micelles. The diblock construct possesses good cell penetrating capabilities and effectiveness to kill SK-MEL-28 melanoma tumor cells, in contrast to reduced intracellular uptake and low cytotoxicity exhibited by the bolaamphiphilic form. Our findings demonstrate that amphipathic design is a relevant variable for self-assembling SLPs to modulate different cellular responses and may assist in optimizing the production of nanostructures based on arginine-enriched sequences in cell penetrating and antimicrobial peptides.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/90472
Identification Number/DOI	10.1039/c9tb02219h
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	Royal Society of Chemistry
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