Fig. 2.

Interaction with the plasma membrane and endocytic uptake of TiO₂ NPs. a Interaction of TiO₂ agglomerates/aggregates with the outer leaflet of the plasma membrane accompanied by the formation of membrane invaginations. The asterisk (*) adverts to a comparatively smaller plasma membrane invagination, which was observed at the site of NP-membrane interaction. b and c TiO₂ NP agglomerates/aggregates of comparable size (0.25 and 0.2 μm in b and c, respectively), but in different relative orientation to the plasma membrane (horizontal and vertical to the plane of the plasma membrane, respectively). d Induction of plasma membrane invagination by a large (> 100 μm) agglomerate/aggregate. The boxed-in area in d is displayed at higher magnification and different brightness and contrast at its right side. It demonstrates that the plasma membrane invagination occurs at the site where an individual NP being associated with the agglomerate/aggregates enters in contact with the cell surface. e TEM image taken 30 min after cell treatment showing TiO₂ NP agglomerates/aggregates inside intracellular vesicles located in the apical cell periphery. The inserts (i and ii) in the upper left part of the image show the boxed-in areas at higher magnification. Sectioning was carried out perpendicular to the plane of the growth surface, which is indicated by the dotted line. The black structure in the middle of the micrograph, which is marked with a hashtag (#) is an artifact owed to a wrinkle in the ultrathin section. PM plasma membrane, PMI plasma membrane invaginations, MT mitochondrion, EE early endosome, NC nucleus. Scale bars: a, b, and c = 0.2 μm; d = 0.5 μm; and e = 2 μm