Mechanical tuning of virus-like particles

Area of Science:

• Biophysics
• Vaccine Development
• Nanotechnology

Background:

• Virus-like particles (VLPs) are emerging as potent scaffolds for mucosal vaccine development.
• Optimal VLP performance may depend on biophysical properties beyond immunological design parameters.

Purpose of the Study:

• To investigate the mechanical properties of Acinetobacter phage AP205 virus-like particles (VLPs).
• To determine how surface modifications, such as polyethylene glycol attachment or antigenic peptide fusion, affect VLP biophysical characteristics.

Main Methods:

• Atomic force microscopy (AFM) was employed to assess VLP mechanical properties.
• Small-angle X-ray scattering (SAXS) provided insights into VLP structure.
• Mechanical properties including stiffness and elastic modulus were quantified.

Main Results:

• AP205 VLPs exhibit significant stiffness (93 ± 23 pN/nm) and an elastic modulus of 0.11 GPa.
• Polyethylene glycol conjugation reduced stiffness to 46 ± 10 pN/nm and elastic modulus to 0.05 GPa.
• Fusion of SARS-CoV-2 spike protein peptides increased stiffness to 146 ± 54 pN/nm, without altering elastic modulus.

Conclusions:

• Surface conjugation strategies can significantly modulate the biophysical properties of VLP scaffolds.
• Changes in VLP mechanical properties are linked to variations in shell thickness and coat protein net charge.
• Understanding and controlling these biophysical properties is crucial for optimizing VLP-based vaccine efficacy.