Biomedical Engineering Reference
In-Depth Information
Rapid plasma protein deposition on material surfaces, which takes place
within seconds,
3
is generally regarded as a universal event that occurs
during protein/surface interactions. The kinds and amounts of proteins
vary depending on the physiochemical properties of the surfaces. Protein
exchange may also occur. The key steps in thrombosis are the formation of
a fi brin clot after the activation of the coagulation cascade and the adhesion,
activation and aggregating of blood platelets. Fibrinogen plays a central role
in both processes.
4
It has been suggested that plasma proteins undergo non-covalent struc-
tural transition (conformational changes) during adsorption to a bioma-
terial surface.
5,6
The term 'post-adsorptive transition' has been coined to
describe the existence of the multiple 'states' of adsorbed protein. Even
though fi brinogen is the third most abundant protein in blood plasma after
albumin and immunoglobulin (IgG),
4,7,8
it plays an important role in throm-
bus formation at areas of relatively low shear.
9
Additionally, fi brinogen dis-
plays unusual adsorption behavior in which the adsorbed protein mass does
not increase in line with the bulk protein concentration. Rather, maximum
adsorption occurs at intermediate dilution of plasma.
5,6,10
In order to better understand the detailed mechanisms responsible for
thrombus formation, the structure/function relationship that leads to the
surface interactions among platelet and plasma proteins, especially fi brin-
ogen, must be elucidated at the molecular level. Atomic force microscopy
(AFM), also know as scanning force microscopy, is a technique that allows
imaging of a molecule in three dimensions under physiological environment
at the molecular level.
11-15
Resolution is routinely on a nanometer scale and
in some cases, sub-nanometer resolution is attained.
16-18
Although the res-
olution is usually up to about 10 nm for biological specimens, this is still far
better than light microscopy.
19
The central hypothesis is that fi brinogen/surface interactions facilitate
thrombogenesis through adhesive platelet binding. Thus, surface-induced
thrombosis involves protein and cell interactions, both with surfaces and
among themselves, which are dominated by intermolecular forces.
6.2
Process and changes during protein adsorption
For hydrophobic surfaces, the main driving force is believed to be hydro-
phobic interaction, in which the protein unfolds its hydrophobic core and/or
uses its hydrophobic domains to adsorb on the surface.
5,6,20-23
Dehydration
between the protein and adsorbent is very likely in order to minimize the
exposure of the hydrophobic domain to the aqueous medium. Post-adsorptive
structural rearrangement probably accompanies the process.
For charged surfaces, either acquired by association or dissociation of sur-
face groups (e.g. carboxylate group), or adsorption of low molecular ions
