Graphene Quantum Dots Modulate Stress Granule Assembly and Prevent Abnormal Phase Transition of Fused in Sarcoma Protein

Abstract

Protein liquid−liquid phase separation (LLPS) plays a crucial role in mediating dynamic assembly of different membraneless organelles such as stress granules (SGs). Dysregulation of dynamic protein LLPS leads to aberrant phase transition and amyloid aggregation which is closely associated with neurodegenerative diseases. In this study, we found that three types of graphene quantum dots (GQDs) exhibit potent activity in preventing SG formation and promoting SG disassembly. We next demonstrate that GQDs can directly interact with the SGs-containing protein fused in sarcoma (FUS), inhibit and reverse FUS LLPS, and prevent its abnormal phase transition. Moreover, GQDs display superior activity in preventing amyloid aggregation of FUS and disaggregating preformed FUS fibrils. Mechanistic study further demonstrates that GQDs with different edge-site exhibit distinct binding affinity to FUS monomers and fibrils, which accounts for their distinct activities in modulating FUS LLPS and fibrillation. Our work reveals the potent capability of GQDs in modulating SG assembly, protein LLPS, and fibrillation and sheds light on rational design of GQDs as effective modulators of protein LLPS for therapeutics application.

Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus

“…We firstly sought to examine the ability of amino and hydroxy-functionalized GQDs (GQDs-NH 2 and GQDs-OH), which was previously found to exhibit a potent activity in preventing condensation of the FUS protein 20 , in modulating phase separation of TDP-43 (Supplementary Fig. 1a, b ).…”

“…However, it is important to note that GQDs-NH 2 and GQDs-OH were unsuccessful in restricting the formation of NBs induced by arsenite stress in cells overexpressing the TDP-43 HA plasmid (Supplementary Fig. 2g, h ), possibly due to their limited ability to penetrate the nucleus compared to their effective entry into the cytoplasm cytoplasmic 20 .…”

High Quantum Yield Amino Acid Carbon Quantum Dots with Unparalleled Refractive Index

“…Bright yellow CQDs have been synthesized with quantum yields up to 71% via an alkali-catalyzed molecular fusion strategy, red CQDs with graphitic carbon nitride have been synthesized using a facile coupling technique, and oxygen-doped carbon dots (O-CDs) that exhibit excellent performance as electrocatalysts have also been synthesized. Recently, Zhang et al have also synthesized three types of graphene-based CQDs, which can be used to prevent single-layer formation and can directly interact with single-layer-containing protein . Furthermore, an EDC/NHS-assisted linking strategy was used to synthesize amide-based carbon quantum dots for heterojunction photocatalysis to enhance charge separation in heterojunction photocatalysts .…”

The gut microbiome meets nanomaterials: exposure and interplay with graphene nanoparticles

“…12 Nano-stem cell therapy holds promise to cure Parkinson's disease, 13 and graphene-based treatment directly affecting proteinopathies is also projected. 14 Despite these advantages, there are also concerns about potential health risks and the influence graphene may have on the human body. Taking into consideration different routes of exposure to graphene-based nanoparticles, like oral, transdermal, and nasal inhalation, various tissues or cells might be affected.…”