Fig. 8: A proposed scheme for FCN2-mediated opsonization of PMOXA- and PEOXA-coated NPs.

a In both human and pig serum, C1q is mostly involved in complement triggering and iC3b opsonin deposition on the surface of NPs. In pig serum also FCN2 is acting as a dominant opsonin (left). Functionally, FCN2 appears more relevant for the uptake of NPs by blood monocytes in pig serum, while the uptake by pig macrophages is less FCN2 and more C1q/iC3b dependent. In the HS, C1q-dependent C3 opsonization is sufficient to ensure macrophage recognition of NPs (right). However, for NP uptake by monocytes, there is interindividual variability with respect to FCN opsonization (red text). b Simplified representation of the promiscuous binding ability of FCN2, ensuring its association with both microbially-displayed GlcNAc (1) and PMOXA or PEOXA (2) due to the recognition of sugar N-acetyl or polymer N-alkyl groups by the S2 sites present in its COOH-terminal fibrinogen-like domains driven by hydrophobic interactions, and to hydrogen bonds with the –OH, -O-, and carbonyl moieties in the GlcNAc, and the carbonyls in PMOXA/PEOXA. Depiction in (3) indicates the hypothetical recognition of other PAMPs (pathogen-associated molecular patterns), DAMPs (damage-associated molecular patterns), and nanomaterial coatings by FCN2 resulting from the identification of regularly displaced aliphatic/hydrophobic and hydrogen bond-forming chemical groups. Red and black circles indicate chemical moieties forming regular patterns on FCN2 targeted molecules, involved in aliphatic and hydrogen bonds, respectively.