Engineering protein nanocages as carriers for biomedical applications

Bhaskar, Sathyamoorthy; Lim, Sierin

Self-assembling polypeptides are created by leveraging natural protein oligomerization domains to form higher-order structures. The interfacing surfaces of these domains can be tuned for assembly into tetrahedral and octahedral structures. 1 Yeates Group leverages on symmetry in designing novel protein cages. 33, 34 Two or more subunits are fused in a geometrically predefined manner which subsequently self-assemble into highly symmetrical structures ( Figure 6 ). 35 The design principles have led to the production of megadalton protein nanocages with icosahedral symmetry. 36 Gradišar et al. 37 proposed a different strategy inspired by DNA origami approach. polyhedral structures consisting of individual self-assembling polypeptide nanostructures based on modularized orthogonal dimerizing segments. The formation of these dimerizing segments is controlled by electrostatic and hydrophobic interactions that serve as a platform for designing new artificial polypeptide folds (Figure 7 ). 37 The interlinked coiled-coil segment-based design can lead to asymmetric structures that are