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

Lucas R. Mello; Rodrigo B. Aguiar; Renata Y. Yamada; Jane Z. Moraes; Ian W. Hamley; Wendel A. Alves; Mehedi Reza; Janne Ruokolainen; Emerson R. Silva

doi:10.1039/C9TB02219H

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

Lucas R. Mello,^a Rodrigo B. Aguiar,^a Renata Y. Yamada,^a Jane Z. Moraes,^a Ian W. Hamley,

^b Wendel A. Alves,

^c Mehedi Reza,^d Janne Ruokolainen^d and Emerson R. Silva

*^a

Author affiliations

* Corresponding authors

^a Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil
E-mail: er.silva@unifesp.br

^b Department of Chemistry, University of Reading, Whiteknights, Reading, UK

^c Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, Brazil

^d Nanomicroscopy Center, Aalto University, Puumiehenkuja 2, FIN-02150 Espoo, Finland

Abstract

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.

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DOI: https://doi.org/10.1039/C9TB02219H
Article type: Paper
Submitted: 09 Oct 2019
Accepted: 21 Feb 2020
First published: 22 Feb 2020

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J. Mater. Chem. B, 2020,8, 2495-2507

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

L. R. Mello, R. B. Aguiar, R. Y. Yamada, J. Z. Moraes, I. W. Hamley, W. A. Alves, M. Reza, J. Ruokolainen and E. R. Silva, J. Mater. Chem. B, 2020, 8, 2495 DOI: 10.1039/C9TB02219H

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Journal of Materials Chemistry B

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

Abstract

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

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