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An Engineered Multivalent TMV Nanodisk Platform for Modulating Integrin Clustering and Cell Signaling.

Haobo He1,2, Yihao Zhou2, Mingming Du2

  • 1School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei, 230026, China.

Angewandte Chemie (International Ed. in English)
|June 4, 2025
PubMed
Summary
This summary is machine-generated.

A novel tobacco mosaic virus (TMV) nanodisk platform enables stable multivalent ligand display, enhancing receptor clustering for cell signaling and osteoarthritis treatment.

Keywords:
IntegrinMultivalenceOsteoarthritis receptor clusterTobacco mosaic virus

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Area of Science:

  • Biochemistry
  • Materials Science
  • Biotechnology

Background:

  • Cell-surface receptor clustering is crucial for cellular signaling and function.
  • Multivalent ligands are valuable for therapeutic strategies but challenging to design.
  • Uniform, stable, and modifiable multivalent ligand scaffolds are needed.

Purpose of the Study:

  • To develop a novel, stable, and uniformly structured protein-based platform for multivalent ligand display.
  • To assess the platform's stability and its efficacy in receptor clustering and therapeutic applications.

Main Methods:

  • Engineered tobacco mosaic virus (TMV) coat protein into a discoid nanodisk scaffold.
  • Introduced T103C modification for enhanced structural stability.
  • Generated multivalent TMV-SPPEPS using an integrin-binding peptide.
  • Evaluated TMV-SPPEPS affinity, integrin clustering, and therapeutic effects in a rat osteoarthritis model.

Main Results:

  • The TMV nanodisk platform demonstrated exceptional stability across a wide pH range and long-term storage.
  • TMV-SPPEPS showed a 453-fold increase in integrin affinity compared to the monomeric peptide.
  • The platform effectively induced cell-surface integrin clustering, promoting mesenchymal stem cell chondrogenesis.
  • TMV-SPPEPS significantly alleviated osteoarthritis in a rat model.

Conclusions:

  • The modified TMV nanodisk serves as a versatile and stable scaffold for multivalent ligand display.
  • This platform effectively controls receptor clustering and modulates intracellular signaling.
  • The TMV nanodisk platform holds significant potential for diverse biomedical applications, including osteoarthritis therapy.