Biomedical Engineering Reference
In-Depth Information
(a)
(b)
Apical surface
1
2
3
Microvilli
Legend
Basolateral surface
Nucleus
Lysosome
FIGURE 13.4 ( See color insert. ) (a) Diagram illustrating substantial routes of epithelial transport. An epi-
thelium is polarized into an apical and basolateral surface with the apical surface covered with microvilli to
increase the surface area for absorption. Nuclei and other organelles inside the cell are also polarized with the
nuclei polarized closer to the basolateral surface. In between the cells, tight junctions and adherent junctions
are present at the apical surface that inhibit the free flow of materials between the apical and basolateral spaces
and provide for epithelial integrity. The nanomaterials can flow between the apical and basolateral spaces if
(1) epithelial integrity is disrupted (pathway 1), (2) cells within the epithelium are killed, providing holes for
the flow of particles (pathway 2), and (3) nanomaterials are moved by transcytosis—a cellular process where
materials are picked up at the apical surface and transported to the basolateral surface without being metabo-
lized by the cell (pathway 3). (b) Diagram of cells in the Transwell chamber. Cells are shown on a membrane
support, which permits the partitioning of the apical and basolateral chambers for measurements of electrical
resistance. Red squares represent tight junctions and blue ellipses represent adherent junctions.
through endothelial cells (Wang et al. 2009). For the GI tract, however, this type of uptake is not
crucial. Absorption-dependent transcytosis is mediated by the interaction of positively charged sub-
stances with anionic sites of the plasma membrane: Cationic NPs had a greater potential than neu-
tral or negatively charged NPs (Harush-Frenkel et al. 2008). In addition, uncoated, not positively
charged TiO 2 NPs can cross the intestinal epithelium by the transcellular route (Koeneman et al.
2010).
There are three pathways by which nanomaterials could cross the epithelial layer as illustrated
in Figure 13.4a. Nanomaterials could disrupt the junctional complexes without killing cells in the
epithelial sheet and pass across the epithelial layer (arrow 1). Nanomaterials could kill cells within
the epithelial sheet and pass through holes formed by dead cells (arrow 2). It is also possible that
nanomaterials could make use of the transport function of epithelial cells used in nutrient uptake
and pass through individual epithelial cells by transcytosis (arrow 3). All three of these possible
routes of transport have been investigated.
One function of epithelial cells of the intestine is to undergo transcytosis. Transcytosis is a pro-
cess whereby extracellular components are endocytosed on one side of the cell; in this case, the api-
cal surface is exposed to the lumen of the gut, and exocytosed from the other surface of the cell, the
basolateral surface where the circulatory system is present, without undergoing metabolism inside
the cell. TiO 2 may be transported across the epithelium without disrupting epithelial integrity if it is
transcytosed (Koeneman et al. 2010).
13.4 BEHAVIOR AND FATE OF NANOMATERIALS IN THE GI TRACT
Whether it exists as nanostructure food ingredient, nanosized particles, or nanocarriers incorpo-
rated in food packaging, human exposure to nanomaterials present in the food or food contact
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