Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides.,Journal of Materials Chemistry B

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Amphipathic design dictates self-assembly, cytotoxicity and cell uptake of arginine-rich surfactant-like peptides.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-02-28 , DOI: 10.1039/c9tb02219h
Lucas R Mello ₁ , Rodrigo B Aguiar ₁ , Renata Y Yamada ₁ , Jane Z Moraes ₁ , Ian W Hamley ₂ , Wendel A Alves ₃ , Mehedi Reza ₄ , Janne Ruokolainen ₄ , Emerson R Silva ₁

Affiliation

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.

中文翻译：

两亲性设计指示富含精氨酸的表面活性剂样肽的自组装，细胞毒性和细胞摄取。

两亲性是表面活性剂样肽（SLP）自组装中最关键的参数，它调节疏水性吸引力将肽结合在一起的方式。它的作用超出了超分子组装，还可能触发基于生物活性肽的纳米结构的不同细胞反应。在本文中，我们研究了基于由精氨酸（R）和苯丙氨酸（F）组成的异构SLP的纳米结构的自组装和细胞效应。研究了两个两亲性设计：二嵌段构建体F4R4及其双亲两亲物类似物R2F4R2。出现强的序列依赖性多态性，并出现小球和囊泡状装配体，或扁平纳米带和圆柱形胶束。双嵌段构建体具有良好的细胞穿透能力和杀伤SK-MEL-28黑色素瘤肿瘤细胞的功效，与之相反，嗜血两亲形式表现出的细胞内摄取减少和低细胞毒性。我们的发现表明，两亲性设计是自组装SLP调节不同细胞反应的相关变量，并且可能有助于优化基于穿透细胞和抗菌肽中精氨酸富集序列的纳米结构的生产。

更新日期：2020-03-26

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