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Virus-like Particles Armored by an Endoskeleton.

Zhuohong Wu1,2,3,4, Jorge L Bayón1,2,3,4, Tatiana B Kouznetsova5

  • 1Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States.

Nano Letters
|January 31, 2024
PubMed
Summary

Researchers developed an endoskeleton-armored strategy to enhance virus-like particle (VLP) stability. This method significantly improves thermal, chemical, and mechanical resistance for VLP-based materials.

Keywords:
cross-linkingprotein cagesingle-molecule force spectroscopystabilizationvirus-like particles (VLPs)

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Area of Science:

  • Biotechnology
  • Materials Science
  • Virology

Background:

  • Virus-like particles (VLPs) offer potential for materials applications due to inherent stability.
  • Current VLP stability limitations hinder commercialization and broader use in advanced materials.
  • Enhancing VLP stability is crucial for expanding their applications in nanotechnology and medicine.

Purpose of the Study:

  • To develop and demonstrate a novel strategy for significantly enhancing the stability of virus-like particles (VLPs).
  • To investigate the impact of internal structural reinforcement on VLP resistance to various physical and chemical stressors.
  • To explore the potential of endoskeleton-armored VLPs for advanced material development.

Main Methods:

  • Developed an 'endoskeleton-armored' strategy by creating an internal polymer backbone within VLPs.
  • Utilized maleimide-PEG15-maleimide cross-linker to covalently link viral coat proteins inside the capsid.
  • Tested the stability of engineered VLPs (PhMV and Qβ) under thermal, chemical, and mechanical stress using various assays and single-molecule force spectroscopy.

Main Results:

  • Endoskeleton-armored VLPs demonstrated significantly improved thermal stability, withstanding 95 °C for 15 minutes.
  • Engineered VLPs exhibited enhanced resistance to a range of denaturants, including surfactants, varying pH levels, chemical denaturants, and organic solvents.
  • Single-molecule force spectroscopy revealed a 6-fold increase in rupture distance and a 1.9-fold increase in rupture force for endoskeleton-armored PhMV VLPs.

Conclusions:

  • The endoskeleton-armored strategy effectively enhances the stability of virus-like particles.
  • Improved VLP stability opens new avenues for the development of robust VLP-based materials.
  • This approach provides greater opportunities for the application of VLPs in diverse fields requiring stable biomaterials.