Biomedical Engineering Reference
In-Depth Information
doses [4]. Consequently, screening techniques commonly used for toxicity testing of macroscale
substances may not be appropriate for NPs hazard characterization, but may have to be adapted or
modified with regard to their nanospecific properties [5].
To facilitate a faster risk assessment of NPs, the use of
in vitro
studies has been suggested as
a widely acceptable approach to evaluate the toxicity of nanomaterials [6]. Numerous
in vitro
studies investigating the cytotoxic, oxidative stress, and inflammation potential of nanomaterials
are now published, although their value for predicting
in vivo
toxicity still remains to be demon-
strated [7].
19.2
INTERACTION OF NP
s
WITH CELLS
19.2.1 I
NterfereNce
of
Np
s
to
c
ells
M
eMBraNe
Cell membranes, which are phospholipid bilayers, partition different intracellular compartments
from extracellular compartments. They also encapsulate the different intracellular components. To
facilitate exchanges of ions, molecules, and NPs between compartments and/or cells, membranes
have to be permeable. The outer surface of the cell membrane that presents toward the extracellular
compartment, allows selective transport of ions, molecules, and also NPs. Intracellular membranes
separate distinct compartments such as mitochondria, vesicles, nucleus, and so on from the cytosol
[8]. The stability of the membrane can be affected by NPs in two ways: either directly (e.g., physical
damage) or indirectly (e.g., oxidation) that can lead to cell death. It is the ability of membranes to
control intracellular homeostasis, through selective permeability and transport mechanisms, which
makes them a vulnerable target for the possible damaging effects of NPs. Interactions of NPs with
membranes largely depend on the NPs' surface properties. Therefore, the surface modifications of
NPs are crucial in the design of drug-delivery systems to enhance uptake into cells [8]. NP size also
plays an important role as it influences surface pressure and adhesion forces [9].
Research has shown that different nanomaterials can damage membranes by various processes
(Figure 19.1) that lead to a compromise of membrane integrity, stability, and the formation of
nanosized holes [10]. The physicochemical properties of NPs seem to be primarily responsible for
changes in membrane morphology and stability [10]. Mitochondria emerge to be a major target
for fullerenes [11] and carbon nanotubes (CNTs) [12]. However, other NPs (e.g., titanium dioxide,
CNTs, polystyrene, silver, etc.) also seem to be able to alter mitochondrial function, leading to apop-
tosis [13,14]. Another preferential intracellular compartment is that of lysosomes, the cell's digestive
system, where the NPs generally end up and the lysosomes try to either digest or excrete them [15].
The impact of size and shape of the nanomaterial on the ability of lysosomes to digest or excrete
NPs is not fully understood.
19.2.2 e
ffect
of
Np
s
to
p
roteINs
aNd
M
acroMolecules
The cell apparatus consists of a large amount of proteins and other macromolecules. These exist in
the form of enzymes (e.g., gastrin), cell-signaling molecules (e.g., hormones), or structural proteins
(e.g., tubulin). Their normal functioning is therefore essential for all vital cellular activities. Correct
molecular conformation is essential for proteins to work as intended. The slight conformational
changes of protein can alter or destroy its function. During their assembly process, chaperones play
an important role in controlling the manner in which proteins fold [16], to obtain a certain confor-
mation. NPs that can be of the same size of protein molecules are able to impede with cell-signaling
processes [17] or interact with proteins [18], either by chaperone-like activity [19] or by changing the
configuration of peptides in forms of aggregation and fibrillation [20]. Protein misfolding and pep-
tide fibrillation leading to amyloid-like structures are associated with neurodegenerative diseases.
Investigating the possible misformation and overproduction of proteins and macromolecules at the
cellular level is important for nanotoxicological considerations [18].
