Beyond icosahedral symmetry in packings of proteins in spherical shells

TL;DR

This study investigates the stability of icosahedral protein cage packings and finds that perturbations often favor disordered structures, suggesting new strategies for designing regular synthetic protein cages.

Contribution

It demonstrates that icosahedral symmetry is not always the most stable configuration under realistic perturbations, informing future protein cage design.

Findings

Disordered structures are more stable than icosahedral packings under certain conditions.

Flexibility in building blocks influences the stability of symmetric packings.

Design strategies can optimize flexibility to achieve regular synthetic cages.

Abstract

The formation of quasi-spherical cages from protein building blocks is a remarkable self-assembly process in many natural systems, where a small number of elementary building blocks are assembled to build a highly symmetric icosahedral cage. In turn, this has inspired synthetic biologists to design de novo protein cages. We use simple models, on multiple scales, to investigate the self-assembly of a spherical cage, focusing on the regularity of the packing of protein-like objects on the surface. Using building blocks, which are able to pack with icosahedral symmetry, we examine how stable these highly symmetric structures are to perturbations that may arise from the interplay between flexibility of the interacting blocks and entropic effects. We find that, in the presence of those perturbations, icosahedral packing is not the most stable arrangement for a wide range of parameters; rather disordered structures are found to be the most stable. Our results suggest that (i) many designed, or even natural, protein cages may not be regular in the presence of those perturbations, and (ii) that optimizing those flexibilities can be a possible design strategy to obtain regular synthetic cages with full control over their surface properties.