Programmable quasisymmetric protein cages from two complementary building blocks

Nature reports a computational design strategy using geometric frustration to create two-component, quasisymmetric protein cages that assemble into sphere-like structures by embedding curvature-inducing pentagonal defects. By pairing complementary trimeric and dimeric blocks, the authors programmably control cage size from ~40 nm to >200 nm and mass from 2 to >50 MDa, comparable to viral capsids. The cages are functionalized for ribonucleoprotein cargo loading and cellular uptake, enabling studies of cargo delivery and size-dependent diffusion in cells. Data and code are publicly available (Zenodo, GitHub), underscoring a new route for biologics delivery and cell biology tools.