Functionalized Graphene as Extracellular Matrix Mimics: Toward Well‐Defined 2D Nanomaterials for Multivalent Virus Interactions

Abstract

Polysulfated nanomaterials that mimic the extracellular cell matrix are of great interest for their potential to modulate cellular responses and to bind and neutralize pathogens. However, control over the density of active functional groups on such biomimetics is essential for efficient interactions, and this remains a challenge. In this regard, producing polysulfated graphene derivatives with control over their functionality is an intriguing accomplishment in order to obtain highly effective 2D platforms for pathogen interactions. Here, a facile and efficient method for the controlled attachment of a heparin sulfate mimic on the surface of graphene is reported. Dichlorotriazine groups are conjugated to the surface of graphene by a one-pot [2+1] nitrene cycloaddition reaction at ambient conditions, providing derivatives with defined functionality. Consecutive step by step conjugation of hyperbranched polyglycerol to the dichlorotriazine groups and eventual conversion to the polyglycerol sulfate result in the graphene based heparin biomimetics. Scanning force microscopy, cryo-transmission electron microscopy, and in vitro bioassays reveal strong interactions between the functionalized graphene (thoroughly covered by a sulfated polymer) and vesicular stomatitis virus. Infection experiments with highly sulfated versions of graphene drastically promote the infection process, leading to higher viral titers compared to nonsulfated analogues.

Scalable Production of Nanographene and Doping via Nondestructive Covalent Functionalization

“…Additional components appear in the C1s spectrum of nGTrz that are assigned to the CN and CN bonds of the triazine functional groups. Furthermore, the N1s spectrum shows two distinct nitrogen species assigned to the nitrogen atoms at the bridge site and in the triazine ring, with a peak area ratio of 1:3 (Figure S5, Supporting Information), similar to previously reported results . Most significantly, NEXAFS results show no noticeable decrease in the content of sp 2 carbon atoms, demonstrating that the π‐conjugated system of nGTrz is preserved (Figure f and Table S2, Supporting Information).…”

“…The height difference between nG and nGTrz, 0.66 ± 0.2 nm, agrees quite closely with the increase predicted by density functional theory modeling, of 0.6–0.7 nm for adding triazine onto both sides of a graphene sheet. This additionally demonstrates the thinner structure of the nG layers as compared to the previously studied thermally reduced graphene oxide sheets, which can be attributed to the exhibited surface chemistry of nG being closer to unmodified graphene sheets.…”

Interactions of Fullerene‐Polyglycerol Sulfates at Viral and Cellular Interfaces

“…Graphene sheets with polyglycerol sulfate coverage strongly interact with herpes simplex, orthopox, and african swine flu viruses . Similar outcomes have also been found for sulfated gold nanoparticles and graphene sheets against vesicular stomatitis virus (VSV).…”

“…VSV is a bullet‐shaped virus that binds to the LDL receptor of host cells via the viral glycoprotein (VSV‐G) . Several studies have implicated a significant role of electrostatic interactions between VSV‐G and nanomaterials or host cell surfaces . However, the role of hydrophobic interactions between these (nano) biointerfaces has not yet been explored.…”

A Water‐Processable and Bioactive Multivalent Graphene Nanoink for Highly Flexible Bioelectronic Films and Nanofibers

“…In order to address the poor aqueous colloidal stability and lack of bioactivity of the graphene nanoink, inspired from the extracellular‐matrix‐/heparin‐mimetic structure reported in our earlier studies, we utilized hyperbranched polyglycerol sulfates (HPGS) as biocompatible and multivalent electrolytes to enhance the aqueous stability of graphene nanoink by repelling π–π stacking interactions and avoiding formation of graphene aggregates during chemical reduction. Meanwhile, the anchored HPGS on graphene can be used as binder to enhance carbon‐to‐carbon and carbon‐to‐substrate interactions.…”