Effect of protein steric constraints on the symmetry of membrane protein polyhedra

Experiments have shown that, in an aqueous environment, lipids and membrane proteins can self-assemble into membrane protein polyhedral nanoparticles (MPPNs). MPPNs are closed, spherical vesicles composed of a lipid bilayer membrane and membrane proteins, with a polyhedral arrangement of membrane proteins. The observed symmetry and size of MPPNs can be understood from the interplay of protein-induced lipid bilayer deformations in MPPNs, topological defects in protein packing necessitated by the spherical shape of MPPNs, and thermal fluctuations in MPPN self-assembly. We explore here the effect of protein steric constraints on MPPN shape. The protein steric constraints considered here may arise from a well-defined shape of protein domains outside the membrane, entropic repulsion between membrane proteins with flexible domains outside the membrane, or binding of other molecules to membrane proteins. Calculating MPPN self-assembly diagrams under protein steric constraints we find that protein steric constraints can strongly affect MPPN self-assembly. Depending on the specific scenario considered, protein steric constraints can leave large portions of the MPPN self-assembly diagrams with no clearly defined MPPN symmetry or substantially expand the regions of MPPN self-assembly diagrams dominated by highly symmetric MPPN states, such as MPPNs with icosahedral or snub cube symmetry. Our results suggest that modification of protein steric constraints may allow the directed self-assembly of MPPNs with specified symmetry, size, and protein composition and may thus facilitate the further utilization of MPPNs for membrane protein structural analysis or targeted drug delivery.