Nanoparticle and Protein Corona - Protein-Nanoparticle Interactions - page 32

hydrophobic polymer chains, forming distinct “islands” which act as protein-
binding sites.
In an earlier work by Moghimi and Patel, an important observation was made
that liposomes rich in cholesterol bind less protein than cholesterol-free liposomes
[ 26 ]. Liposomes composed of neutral saturated lipids with carbon chains greater
than C16 have been reported to bind larger quantities of blood proteins compared
with their C14 counterparts [ 27 ]. This has been explained by stronger affinities of
plasma proteins, especially IgG and albumin for hydrophobic domains. Therefore,
it can be concluded that the affinity of proteins to nanomaterials with uniform
surface chemistry tends to increase with increasing charge density and

hydrophobicity [ 28 ].

2.4.5 Nanoparticle Size

Due to surface curvature, protein-binding affinities are different for NPs and flat
surfaces. Therefore, the protein adsorption data on flat surface should not be
extrapolated for NPs. In addition to protein-binding affinity, the composition of
protein corona is different for same NPs but with different sizes [ 1 ]. The change of
composition and organization of proteins in the corona is very significant when the
nanoparticle size is approaching the size of proteins [ 7 ]. The highly curved surfaces
of nanomaterials decrease protein-protein interactions. Proteins adsorbed to highly
curved nanoparticles tend to undergo fewer changes in conformation than those
adsorbed to less curved surfaces.
Size and curvature of nanoparticles also appear to affect protein binding. For
example, classical IgM-dependent complement activation is most efficient on
dextran particles in the optimal size range, ~250 nm, whereas larger particles do
not attract as much IgM and therefore do not activate to the same extent. The same
phenomenon of size-dependent activation of complement was observed for
liposomes. Dobrovolskaia et al. [ 13 ] reported that more proteins were adsorbed
on 30 nm than on 50 nm gold particles. Lynch et al. [ 7 ] studied the role of particle
size and surface area on the protein adsorption on NIPAM/BAM (50:50) copolymer
nanoparticles. Using nanoparticles varying in size between 70 and 700 nm, they
showed that the amount of bound plasma proteins increased with increasing avail-
able surface area at a constant particle weight. At a constant weight fraction of
nanoparticles, the surface area available for protein binding increases with decreas-
ing particle size. Another study involving the interaction of gold nanoparticles with
common plasma proteins suggests that the thickness of the adsorbed protein layer
increases progressively with nanoparticle size. Gold nanoparticles can initiate
protein aggregation at physiological pH, resulting in the formation of extended,
amorphous protein-nanoparticle assemblies, accompanied by large protein
aggregates without embedded nanoparticles. Proteins on the Au nanoparticle sur-
face are observed to be partially unfolded; these nanoparticle-induced misfolded
proteins likely catalyze the observed aggregate formation and growth.