Analyzing the Biological Entity of Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 62

domain to interact with the nanomaterial (Tenzer et al. 2011). Consequently, adsorp-
tion of a protein can occur in different orientations, which can even lead to a wrap-
ping of proteins around a nanomaterial (Roach, Farrar, and Perry 2006; Shemetov,
Nabiev, and Sukhanova 2012).
Charge-driven adsorption effects are strongly dependent on the pH of the disper-
sion medium and can trigger adsorption effects, too. The adsorption of proteins to
nanomaterials again can alter their zeta-potential, leading to a collapse of repulsive
stabilizing interactions (Shemetov, Nabiev, and Sukhanova 2012). Hydrophobicity
is considered as one of the most important physicochemical parameters of nano-
material surface regarding adsorption of proteins. On the atomic level, the pres-
ence of non-polar functional groups has a large influence on protein adsorption, as
hydrophobic surfaces provoke the exposure of hydrophobic protein cores toward the
nanomaterial surfaces for entropic reasons (Lundqvist et al. 2008; Gessner et al.
2000). Each protein has an intrinsic stability, that is, a thermodynamically favor-
able state. Any additional energy added to the system will cause an alternative
state, being either reversible or irreversible, whereas the latter can be considered
as (partial) denaturation of the protein (Shemetov, Nabiev, and Sukhanova 2012).
Hydrophobicity-driven changes in the secondary structure can expose new epitopes
of a protein toward cells, which potentially cause an immunological response toward
the nanomaterial-protein complex. However, hydrophilic groups can also interact
with proteins via hydrogen bond formation, which in contrast to hydrophobicity-
driven adsorption is less disruptive (Shemetov, Nabiev, and Sukhanova 2012). This
demonstrates that the interaction of proteins with nanoparticle surfaces may also
influence the conformation of proteins, which in turn can influence protein-protein
interactions and then lead to fibrillation, protein aggregation, or similar processes.
For instance, enhanced fibrillation has been shown to occur for β2-microglobulin
when interacting with polymeric nanoparticles (Linse et al. 2007), or suppressed
fibrillation can occur as shown for amyloid-β protein when interacting with the same
nanoparticles (Cabaleiro-Lago et al. 2008). Nanoparticle-protein interaction may
also influence enzymatic activity (Wu, Zhang, and Yan 2009; Chakraborti et al.
2010). Different enzymes may change their activities to different extents when being
adsorbed to nanoparticles. When chymotrypsin was adsorbed onto multiwalled car-
bon nanotubes (MWCNTs), it retained only 1% of its activity whereas peroxidase
retained 30% (Wu, Zhang, and Yan 2009; Karajanagi et al. 2004). In contrast, when
lysozyme was adsorbed onto ZnO nanoparticles, the activity was largely retained
and in addition the enzyme was partially protected against unfolding effects occur-
ring under elevated temperature conditions or when adding chaotropic agents
(Chakraborti et al. 2010). Moreover, some proteins bind in a cooperative manner,
that is, secondary proteins can bind to a nanomaterial-protein complex based on
protein-protein interactions (Walkey and Chan 2012). Especially in complex fluids
this may significantly contribute to not only the formation of the protein corona
with respect to its initial formation but also its evolution over time. For instance, it is
known that in complex biological fluids (e.g., plasma), primarily the highly abundant
proteins bind to a nanomaterial quickly, which is referred to as kinetic formation of
the corona. Later on they can be exchanged over time by proteins with higher affinity
to the nanomaterial, which is then the thermodynamically stable corona. This is also