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Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles

Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles
Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles
The mechanical interactions between virus-like particles and host cells may offer targets for new viral treatments and vaccines with modes of action that are independent of the immune system. The physical properties of structures involved govern the particle-cell interactions. While the mechanical properties of virions and mammalian cells have been widely studied, data on virus-like particles are limited. This study aimed to determine the mechanical and morphological properties of HIV-1 virus-like particles with different envelopes. Three HIV-like particles, i.e. Gagᴹ + gp150, Gagᴹ + gp140HA₂tr, and Gagᴹ + gp120HA₂, were produced by combining the same Gag protein shell with different trimeric glycoprotein envelopes. The particles’ spring constant, breaking force, and dimensions were determined using atomic force microscopy, and the elastic modulus was quantified using finite element analysis. Spring constant, elastic modulus, and breaking force were higher for Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ than for Gagᴹ + gp150. The particle height was smaller for Gagᴹ + gp120HA₂ than for Gagᴹ + gp150 and Gagᴹ + gp140HA₂tr. Possible mechanisms underlying the increase of the particles’ stiffness and mechanical strength are the inclusion of the influenza virus HA transmembrane domain in the HIV Env protein, and the lower expression and packing density of Env in Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ compared to Gagᴹ + gp150 found previously. Upon confirmation, the proposed mechanisms offer potential to tailor the mechanics of HIV virus-like particles and guide mechanical interactions between VLPs and host cells towards improving vaccines.
virus-like particle, Human Immunodeficiency Virus, Finite element modelling, Virion mechanics, Elastic modulus, stiffness
1751-6161
Kruse, Elizabeth
8bf3128a-ddbc-42fb-9e8e-af2f99a07b76
van Diepen, Michiel
7f5a26a9-c6f6-4925-9975-a43abb087754
Chapman, Rosamund
c1b8b03f-61be-45f6-963d-5ee60b1f174b
Horn, Etienne
36041222-fa55-4b31-a868-c150adfccd25
Abdalrahman, Tamer
65d60fa0-5278-4158-9e58-a75854a2c4c1
Williamson, Anna-Lise
ebcc479d-ce96-4d3e-a8bd-8aaa19db9065
Rybicki, Edward P.
607e427a-c417-4753-bd45-449fb519378f
Roos, Wouter H.
7070e9b8-5b44-4837-9bfc-2a937885eaba
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50
Kruse, Elizabeth
8bf3128a-ddbc-42fb-9e8e-af2f99a07b76
van Diepen, Michiel
7f5a26a9-c6f6-4925-9975-a43abb087754
Chapman, Rosamund
c1b8b03f-61be-45f6-963d-5ee60b1f174b
Horn, Etienne
36041222-fa55-4b31-a868-c150adfccd25
Abdalrahman, Tamer
65d60fa0-5278-4158-9e58-a75854a2c4c1
Williamson, Anna-Lise
ebcc479d-ce96-4d3e-a8bd-8aaa19db9065
Rybicki, Edward P.
607e427a-c417-4753-bd45-449fb519378f
Roos, Wouter H.
7070e9b8-5b44-4837-9bfc-2a937885eaba
Franz, Thomas
31f508f4-6851-4274-b256-cc01ab321d50

Kruse, Elizabeth, van Diepen, Michiel, Chapman, Rosamund, Horn, Etienne, Abdalrahman, Tamer, Williamson, Anna-Lise, Rybicki, Edward P., Roos, Wouter H. and Franz, Thomas (2026) Impact of modification of envelope proteins on the mechanical properties of HIV virus-like particles. Journal of the Mechanical Behavior of Biomedical Materials, 178, [107394]. (doi:10.1016/j.jmbbm.2026.107394).

Record type: Article

Abstract

The mechanical interactions between virus-like particles and host cells may offer targets for new viral treatments and vaccines with modes of action that are independent of the immune system. The physical properties of structures involved govern the particle-cell interactions. While the mechanical properties of virions and mammalian cells have been widely studied, data on virus-like particles are limited. This study aimed to determine the mechanical and morphological properties of HIV-1 virus-like particles with different envelopes. Three HIV-like particles, i.e. Gagᴹ + gp150, Gagᴹ + gp140HA₂tr, and Gagᴹ + gp120HA₂, were produced by combining the same Gag protein shell with different trimeric glycoprotein envelopes. The particles’ spring constant, breaking force, and dimensions were determined using atomic force microscopy, and the elastic modulus was quantified using finite element analysis. Spring constant, elastic modulus, and breaking force were higher for Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ than for Gagᴹ + gp150. The particle height was smaller for Gagᴹ + gp120HA₂ than for Gagᴹ + gp150 and Gagᴹ + gp140HA₂tr. Possible mechanisms underlying the increase of the particles’ stiffness and mechanical strength are the inclusion of the influenza virus HA transmembrane domain in the HIV Env protein, and the lower expression and packing density of Env in Gagᴹ + gp140HA₂tr and Gagᴹ + gp120HA₂ compared to Gagᴹ + gp150 found previously. Upon confirmation, the proposed mechanisms offer potential to tailor the mechanics of HIV virus-like particles and guide mechanical interactions between VLPs and host cells towards improving vaccines.

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More information

Accepted/In Press date: 2 March 2026
e-pub ahead of print date: 10 March 2026
Published date: 13 March 2026
Keywords: virus-like particle, Human Immunodeficiency Virus, Finite element modelling, Virion mechanics, Elastic modulus, stiffness

Identifiers

Local EPrints ID: 510610
URI: http://eprints.soton.ac.uk/id/eprint/510610
ISSN: 1751-6161
PURE UUID: 2314633b-03fd-4910-a588-a75a8057b3d6

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Date deposited: 14 Apr 2026 16:35
Last modified: 14 Apr 2026 16:36

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Contributors

Author: Elizabeth Kruse
Author: Michiel van Diepen
Author: Rosamund Chapman
Author: Etienne Horn
Author: Tamer Abdalrahman
Author: Anna-Lise Williamson
Author: Edward P. Rybicki
Author: Wouter H. Roos
Author: Thomas Franz

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