One of the most common reasons for implant failure is immune rejection. Implant
rejection leads to additional surgical intervention and, ultimately, increases health
cost as well as recovery time. Within a few hours after implantation, the implant
surface is covered with host proteins. Adsorption of fibrinogen, a soluble plasma
glycoprotein, is responsible in triggering the immune response to a given material
and, subsequently, in determining its biocompatibility. The work presented here is
focused on modeling the interaction between artificial surfaces and plasma proteins
at the microscopic level by taking into account the physico-chemical properties of
the surfaces. Carbon-based nanomaterials are chosen as a model system due to their
unique bioadhesive and contradictory biocompatible properties as well as the possibility
of functionalization for specific applications. Graphene and its derivatives, such as
graphene oxide and reduced graphene oxide, demonstrate controversial toxicity properties in vitro as well as in vivo. In this study, by covalently adding chemical groups,
the wettability of graphene surfaces and the subsequent changes in its biocompatibility
are being examined. An empirical force field potential (AMBER03) molecular
dynamic simulation code implemented in the YASARA software package was utilized
to model graphene/biomolecule interactions. The accuracy of the force field choice
was verified by modeling the adsorption of individual amino acids to graphene surface
in a vacuum. The obtained results are in excellent agreement with previously
published ab initio findings. In order to mimic the natural protein environment, the
interaction of several amino acids with graphene in an explicit solvent was modeled.
The results show that the behaviour of amino acids in aqueous conditions is drastically different from that in vacuum. This finding highlights the importance of the
host environment when biomaterial-biomolecule interfaces are modeled.
The surface of Graphene Oxide (GO) has been shown to exhibit properties that
are useful in applications such as biomedical imaging, biological sensors and drug
delivery. An assessment of the intrinsic affinity of amino acids to GO by simulating
their adsorption onto a GO surface was performed. The emphasis was placed on
developing an atomic charge model for GO that was not defined before. Next, the
simulation of a fibrinogen fragment (D-domain) at the graphene surface in an explicit
solvent with physiological conditions was performed. This D-domain contains
the hidden (not expressed to the solvent) motifs (PI 7190-202 and P2 7377-395, and
specifically P2-C portion 7383-395) that were experimentally found to be responsible
for attracting inflammatory cells through CDllb/CD18 (Mac-1) leukocyte integrin
and, consequently, promoting the cascade of immune reactions. It was hypothesized
that the hydrophobic nature of graphene would cause critical changes in the fibrinogen
D-domain structure, thus exposing the sequences and result in the foreign body
reaction. To further study this issue, molecular mechanics was used to stimulate
the interactions between fibrinogen and a graphene surface. The atomistic details of
the interactions that determine plasma protein affinity modes on surfaces with high
hydrophobicity were studied. The results of this work suggest that graphene is potentially
pro-inflammatory surface, and cannot be used directly (without alterations)
for biomedical purposes. A better understanding of the molecular mechanisms underlying
the interaction between synthetic materials and biological systems will further
the ultimate goal of understanding the biocompatibility of existing materials as well
as design of new materials with improved biocompatibility
