Graphene Oxide Nanosheets Tailored With Aromatic Dipeptide Nanoassemblies for a Tuneable Interaction With Cell Membranes.

Giuseppe Trapani,Giovanni Tabbì,Francesco Attanasio,Viviana Carmela Linda Caruso,Cristina Satriano,Lorena Maria Cucci,Diego La Mendola,Giuseppe Forte

doi:10.3389/fbioe.2020.00427

Abstract

Engineered graphene-based derivatives are attractive and promising candidates for nanomedicine applications because of their versatility as 2D nanomaterials. However, the safe application of these materials needs to solve the still unanswered issue of graphene nanotoxicity. In this work, we investigated the self-assembly of dityrosine peptides driven by graphene oxide (GO) and/or copper ions in the comparison with the more hydrophobic diphenylalanine dipeptide. To scrutinize the peptide aggregation process, in the absence or presence of GO and/or Cu2+, we used atomic force microscopy, circular dichroism, UV–visible, fluorescence and electron paramagnetic resonance spectroscopies. The perturbative effect by the hybrid nanomaterials made of peptide-decorated GO nanosheets on model cell membranes of supported lipid bilayers was investigated. In particular, quartz crystal microbalance with dissipation monitoring and fluorescence recovery after photobleaching techniques were used to track the changes in the viscoelastic properties and fluidity of the cell membrane, respectively. Also, cellular experiments with two model tumour cell lines at a short time of incubation, evidenced the high potential of this approach to set up versatile nanoplatforms for nanomedicine and theranostic applications.

Highlights

In the past decade, the use of engineered carbon-based nanomaterials for technological applications has attracted much interest in the field of nanomedicine
The mechanisms by which graphene oxide (GO) and reduced GO show toxicity against cells and bacteria include the membrane stress caused by direct contact with sharp nanosheets, ensuing enhanced production of reactive oxygen species (ROS), the loss of plasma membrane structural integrity associated with a strong physical interaction of GO with the phospholipid bilayer (Lammel et al, 2013), apoptosis and autophagy (Jia et al, 2019)
We demonstrate here that the different surface decoration of the graphene-based 2D nanosheets by the two dipeptides allows for a modulated interaction with artificial cell membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) supported lipid bilayers (SLBs)

Summary

INTRODUCTION

The use of engineered carbon-based nanomaterials for technological applications has attracted much interest in the field of nanomedicine. Peptide-based self-assembly offers new routes to fabricate various nanostructures including nanotubes, nanowires, nanospheres, nanofibrils, vesicles and hydrogels (AdlerAbramovich and Gazit, 2014), which are of interest in materials science, energetics and nanomedicine applications (Gan and Xu, 2017; Schnaider et al, 2017; Tesauro et al, 2019) Aromatic amino acids, such as phenylalanine (Phe, F) and tyrosine (Tyr, Y), are known to assemble into helical nanotube or nanofiber structures, through a process mostly driven by π–π stacking, charge transfer and H-bonding (Reches and Gazit, 2003; MenardMoyon et al, 2015). Proofof-work cellular experiments on human tumor (neuroblastoma and prostatic) cells highlighted the promising potential of these platforms for theranostic applications

MATERIALS AND METHODS

RESULTS AND DISCUSSION

DATA AVAILABILITY STATEMENT

CONCLUSION