The difference in the measured zeta potential between PBS and VDB is mainly due to the higher ionic strength in PBS, resulting in a reduced Debye length from increased charge screening. This may induce a more minor change in the zeta potential in PBS upon pMETAC addition (see Figure ). The conductivity measurement also reflects the higher ionic-strength environment in PBS (see Figure ). However, in VDB, at 1:5, the zeta potential is close to 0 mV. The reduction of the zeta potential from 1:0 to 1:5 indicates that electrostatic interaction is the main driving force due to the adsorption of the pMETAC onto the surface of AP205 VLP. Regarding the fact that the system assembles into hcp, one can think that the pMETAC adsorbs isotopically onto the AP205 VLP. AP205 VLP self-assembles into 3D hexagonal structures with pMETAC of similar size, already at lower pMETAC content. The difference in packing occurs likely due to the functional group distributions on the capsid surface and the influence of the RNA on the surface charge. The magnitude of the zeta potential of AP205 VLP of |-8.9 ± 0.6| mV in VDB at pH 7.0, is lower than Qbeta, with |-21.4 ± 1.3| mV. The difference in zeta potential correlates with the lower quantity of pMETAC needed to reduce the electrostatic repulsions to trigger suprastructure formation. The hcp packing of the AP205 VLP is likely a result of a relatively homogeneous distribution of the charged functional groups and its relatively smooth surface, allowing relatively isotropic interactions between the individual particles. Contrary, Qbeta, with a more irregular surface and a "patchy" charge distribution, packs into a 2D hexagonal structure, which requires more anisotropic inter-particle interactions. Those anisotropic interactions have been investigated with Janus-like particles, which have been shown to form a variation of different structures. Complex ordering, such as quasicrystals, can be explained by the principle of patchy surfaces, with varying numbers of patches and directional bonds of different strengths. Therefore, it is likely that the patchiness with charged and hydrophobic areas on the nanocages can induce directional interactions. A hypothesis is that electrostatic interactions are dominant in the direction of charged areas, while in hydrophobic areas, van der Waals interactions are the main driving force. Electrostatic interactions govern the initial interaction because it is present at a longer distance, with a decay of 1/r 2 -1/r 4 , while dispersion forces are driving as secondary rearrangement forces when the particles are closer to each other as it decays with ~1/r 6 . 51