Tuning Viral Capsid Nanoparticle Stability with Symmetrical Morphogenesis.

Virus-like particles (VLPs) provide engineering platforms for the design and implementation of protein-based nanostructures. These capsids are comprised of protein subunits whose precise arrangement and mutual interactions determine their stability, responsiveness to destabilizing environments, and ability to undergo morphological transitions. The precise interplay between subunit contacts and the overall stability of the bulk capsid population remains poorly resolved. Approaching this relationship requires a combination of techniques capable of accessing nanoscale properties, such as the mechanics of individual capsids, and bulk biochemical procedures capable of interrogating the stability of the VLP ensemble. To establish such connection, a VLP system is required where the subunit interactions can be manipulated in a controlled fashion. The P22 VLP is a promising platform for the design of nanomaterials and understanding how nanomanipulation of the particle affects bulk behavior. By contrasting single-particle atomic force microscopy and bulk chemical perturbations, we have related symmetry-specific anisotropic mechanical properties to the bulk ensemble behavior of the VLPs. Our results show that the expulsion of pentons at the vertices of the VLP induces a concomitant chemical and mechanical destabilization of the capsid and implicates the capsid edges as the points of mechanical fracture. Subsequent binding of a decoration protein at these critical edge regions restores both chemical and mechanical stability. The agreement between our single molecule and bulk techniques suggests that the same structural determinants govern both destabilizing and restorative mechanisms, unveiling a phenomenological coupling between the chemical and mechanical behavior of self-assembled cages and laying a framework for the analysis and manipulation of other VLPs and symmetric self-assembled structures.