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 + gp140HA 2 tr, and Gagᴹ + gp120HA 2 , 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 + gp140HA 2 tr and Gagᴹ + gp120HA 2 than for Gagᴹ + gp150. The particle height was smaller for Gagᴹ + gp120HA 2 than for Gagᴹ + gp150 and Gagᴹ + gp140HA 2 tr. 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 + gp140HA 2 tr and Gagᴹ + gp120HA 2 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. • Influenza protein and lower Env expression may raise HIV VLP stiffness and strength • Influenza protein and Env expression likely mechanisms to tailor HIV VLP mechanics • Envelope mechanics can guide VLP design for novel vaccines and targeted therapies
Kruse et al. (Sun,) studied this question.