(B-58) Thermally and Mechanically Stabilized Virus-like Particles via Internal Crosslinking

Many virus-like particles (VLPs) have good chemical, thermal, and mechanical stability compared to other biologics. However, to enable translation and commercialization of VLP-based materials for applications such as drug delivery or in solid-state devices, stability needs improvements. We developed an endoskeleton-enhanced strategy to empower the VLP stability. Specifically, the VLPs of physalis mottle virus (PhMV) and Qbeta (Qβ) were used to demonstrate this concept. We built an internal polymer ‘backbone’ using maleimide–PEG15–maleimide crosslinker to interlink viral coat proteins inside the capsid cavity, while the native VLPs only build on non-covalent bonding. Endoskeleton-armored VLPs exhibited significantly improved thermal stability (95 °C for 15 mins), increased resistance to denaturants (i.e., surfactants, pHs, chemical denaturants, and organic solvent), and enhanced mechanical performance. Single-molecule force spectroscopy demonstrated a 5-fold increase in rupture distance and a 1.7-fold increase in rupture force. Overall, this endoskeleton-enhanced strategy provides more opportunities for materials development and applications.