These different binding phenomena can be rationalized by considering the relative dimensions of both binding partners. The hydrodynamic dimensions of QR-DiMan can be estimated from the average QR core dimensions obtained by S/TEM (core length, 𝐿 core 14.7 ± 5.7 nm; core diameter, 𝐷 core 3.1 ± 0.7 nm; Figure ) and the estimated hydrodynamic surface ligand length (2.9 ± 1.1 nm; derived from the previous QD-DiMan dimensions, 𝐷 ℎ = 9.5 ± 0.1 nm and 𝐷 core = 3.7 ± 2.1 nm). This provided a QR-DiMan estimated terminal end 𝐷 ℎ and cylindrical height (𝐻) of 8.9 ± 2.3 nm and 11.6 ± 5.7 nm, respectively (see SI, Figures and). Both of these dimensions are comparable with that of the equivalent QD-DiMan scaffold (𝐷 h = 9.5 ± 0.1 nm). Due to the flexible nature of the EG11 chains, the surface area and inter-glycan distance of each glycan ligand can be assumed to be roughly the same across the whole QR, i.e. 1.6 nm 2 and 1.4 nm, respectively, for a surface coverage ). This means that the binding contact area of each DC-SIGNR is likely to be smaller than both the spherical and cylindrical regions of the QR, and would cover a QR surface area containing ~20 glycans. These simple calculations suggest that neither the QR size nor the interglycan distance are likely to be the main factor causing the distinct binding mode for DC-SIGNR between the QR end and middle sections. Instead, the distinct DC-SIGNR binding modes are most likely to be determined by the large differences in the 3-dimensional surface curvatures between these regions. In fact, at the spherical ends of the QR, surface curvature could theoretically impart separation distances (𝑑) as much as ~4 nm from the protein binding sites to the glycan surface (eq 3). Where 𝑝 is the Ca-Ca distance between two CRDs at the furthest separation distance from the scaffold surface, which is taken as the average diagonal Ca-Ca distance (𝑝 ~ 8.8 nm; Figure ).