Biomedical Engineering Reference
In-Depth Information
2.3 Dynamic of Protein Corona and Its Time Evolution
The attachment of proteins and lipids from the biological environment results in the
formation of hard and soft coronas with long and short typical exchange times,
respectively. The typical lifetime of hard corona has been shown to be many hours
[
1
]. The hard corona lifetime is long enough for many biological and physiological
phenomena, and therefore, this hard corona defines the biological identity of the
particle. The competition between more than 3,700 proteins in the blood plasma for
adsorption on the surface of the nanoparticle changes the composition of the corona
over time [
7
]. Therefore, corona is not a fix layer, and its composition is determined
by the kinetic rate of adsorption and desorption of each protein and lipid (Fig.
2.1
).
In most of the cases, proteins with high abundance in the plasma are adsorbed on the
surface, and over the time, they are replaced by proteins with lower concentration
but higher affinity.
Recently the protein corona formation has been studied on FePt and CdSe/ZnS
[
12
] and Au nanoparticles [
13
]. The protein absorption has been measured after
5-30 min incubation time, showing that the adsorption of blood serum proteins to
an inorganic surface is time dependent. The highest mobility proteins arrive first
and are later replaced by less mobile proteins that have a higher affinity for the
surface. This process may take several hours. As shown by Slack and Horbett, this
process is the general phenomenon governing the competitive adsorption of a
complex mixture of proteins (as serum) for a given number of surface sites [
14
].
Cedervall et al. [
15
] modeled plasma protein adsorption using a bi-exponential
function. This model distinguishes protein adsorption and desorption into “fast” and
“slow” components. During plasma protein adsorption to copolymer nanoparticles,
the fast component (hard corona) is formed in seconds, while the slow component
(soft corona) builds on a time scale of minutes to hours. Desorption shows similar
behavior with a mean lifetime of about 10 min for the fast component (soft corona)
and about 8 h for the slow component (hard corona). Similar kinetic behavior can be
applied to plasma protein adsorption to other nanomaterials. The hard corona is
probably more important than the soft corona in determining the physiological
response. As a result of its long residence time, the hard corona remains adsorbed to
a nanomaterial during biophysical events such as endocytosis.
Proteins adsorbed to a nanomaterial are in a continuous state of dynamic
exchange. At any time, a protein may desorb, allowing other proteins to interact
on the nanoparticle surface. These changes in the composition of the protein corona
resulting from desorption/adsorption are known as the “Vroman effect.” This effect
takes into account that the identities of the adsorbed proteins can change over time
even if the total amount of adsorbed protein remains roughly constant. During the
initial formation of the protein corona, proteins with the highest association rates
adsorb to a nanomaterial. If these proteins have short residence times, they will be
replaced with other proteins that may have slower association rates but longer
residence times. During plasma protein adsorption, the Vroman effect can be
divided into “early” and “late” stages. The early stage involves the rapid adsorption
