Fig. 2

Active and passive cellular uptake pathways for ENMs in eukarotic cells. Passive uptake occurs via diffusion and facilitated diffusion via transport proteins, i.e. gated channel proteins and carrier proteins. Active uptake pathways involve transmembrane carrier proteins and endocytic pathways including receptor-mediated phagocytosis, clathrin-mediated endocytosis (120 nm, via clathrin-coated pits) and caveolae-mediated endocytosis (60 nm, via lipid rafts), non-specific endocytosis by macropinocytosis and non-clathrin, non-caveolae endocytosis (90 nm, fluid phase). All pathways except caveolae-mediated endocytosis and diffusion merge with the lysosomal degradation system comprising numerous vesicle maturation steps within the cell. A lysosome typically ranges from 200 to 500 nm in diameter. Phagocytosis is mediated by specific membrane-receptors that are activated upon contact with a ligand to produce phagosomes (>250 nm). During their maturation process, phagosomes transform into late phagosomes, which fuse with lysosomes to form phagolysosomes. During macropinocytosis, internalisation occurs via an unspecific invagination resulting in pinocytic vesicles (<150 nm), which eventually merge with lysosomes. Clathrin-mediated endocytosis and non-clathrin, non-caveolae-mediated endocytosis produces caveosomes that either transfer their contents into the Golgi apparatus, endoplasmatic reticulum (ER) or into the cytosol or may also undergo transcytosis.