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Virus-like Particles Armored by an Endoskeleton.

Authors
  • Wu, Zhuohong1, 2, 3, 4
  • Bayón, Jorge L1, 2, 3, 4
  • Kouznetsova, Tatiana B5
  • Ouchi, Tetsu5
  • Barkovich, Krister J2, 3, 4, 6
  • Hsu, Sean K2, 3, 4, 7
  • Craig, Stephen L5
  • Steinmetz, Nicole F1, 2, 3, 4, 6, 7, 8, 9, 10
  • 1 Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 2 Center for Nano-ImmunoEngineering, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 3 Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 4 Shu and K. C. Chien and Peter Farrell Collaboratory, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 5 Department of Chemistry, Duke University, Durham, North Carolina 27708, United States. , (United States)
  • 6 Department of Radiology, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 7 Department of Molecular Biology, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 8 Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 9 Institute for Materials Discovery and Design, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
  • 10 Center for Engineering in Cancer, Institute for Engineering in Medicine, University of California, San Diego, La Jolla, California 92093, United States. , (United States)
Type
Published Article
Journal
Nano Letters
Publisher
American Chemical Society
Publication Date
Mar 13, 2024
Volume
24
Issue
10
Pages
2989–2997
Identifiers
DOI: 10.1021/acs.nanolett.3c03806
PMID: 38294951
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Many virus-like particles (VLPs) have good chemical, thermal, and mechanical stabilities compared to those of other biologics. However, their stability needs to be improved for the commercialization and use in translation of VLP-based materials. We developed an endoskeleton-armored strategy for enhancing VLP stability. Specifically, the VLPs of physalis mottle virus (PhMV) and Qβ were used to demonstrate this concept. We built an internal polymer "backbone" using a maleimide-PEG15-maleimide cross-linker to covalently interlink viral coat proteins inside the capsid cavity, while the native VLPs are held together by only noncovalent bonding between subunits. Endoskeleton-armored VLPs exhibited significantly improved thermal stability (95 °C for 15 min), increased resistance to denaturants (i.e., surfactants, pHs, chemical denaturants, and organic solvents), and enhanced mechanical performance. Single-molecule force spectroscopy demonstrated a 6-fold increase in rupture distance and a 1.9-fold increase in rupture force of endoskeleton-armored PhMV. Overall, this endoskeleton-armored strategy provides more opportunities for the development and applications of materials.

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