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Related Experiment Video

Updated: May 27, 2025

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Graphene Biosensor Differentiating Sensitive Interactions between Ribonucleic Acid and Dipeptide Repeats in

Kantaro Kikuchi1, Yui Yamazaki1, Kohsuke Kanekura2

  • 1Department of Materials Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, Tokyo 152-8550, Japan.

ACS Applied Materials & Interfaces
|February 17, 2025
PubMed
Summary

Graphene field-effect transistors detect interactions between disease-linked peptides and RNA at nanomolar concentrations. This advances understanding of liquid-liquid phase separation in neurodegenerative diseases like ALS and FTD.

Keywords:
biosensordipeptide repeat proteinsgraphene field-effect transistorliquid−liquid phase separationmolecular interactions

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Area of Science:

  • Biophysics
  • Neuroscience
  • Materials Science

Background:

  • Liquid-Liquid Phase Separation (LLPS) is vital in cell biology and implicated in neurodegenerative diseases such as ALS and FTD.
  • Mutations in C9ORF72 gene produce arginine-rich dipeptide repeat proteins (R-DPRs) that disrupt LLPS and contribute to disease pathology.
  • Existing methods struggle to detect weak intermolecular interactions within LLPS droplets.

Purpose of the Study:

  • To utilize graphene field-effect transistors (GFETs) for sensitive detection of molecular interactions in LLPS.
  • To investigate the interaction mechanisms between R-DPRs and RNA.
  • To explore the role of peptide properties, like proline-induced rigidity, in LLPS.

Main Methods:

  • Immobilization of RNA (poly-A) onto GFETs.
  • Measurement of GFET electrical conductivity to detect shifts in the charge neutral point.
  • Characterization of interactions with dipeptide repeat peptides (poly(PR), poly(GR), R12) at varying concentrations.

Main Results:

  • GFETs detected peptide-RNA interactions at nanomolar concentrations, significantly improving sensitivity over traditional methods.
  • Interactions were dependent on peptide concentration and varied between different peptide types.
  • Peptides with proline residues showed nonuniform spatial distribution, indicating proline-induced rigidity influences RNA interactions.

Conclusions:

  • GFETs offer a highly sensitive platform for studying molecular interactions relevant to LLPS and neurodegenerative diseases.
  • Peptide rigidity, particularly from proline residues, plays a key role in multivalent interactions with RNA.
  • This research provides new insights into the mechanisms of R-DPRs in LLPS and disease pathogenesis.