ci5b00703_si_001.pdf (6.42 MB)
Molecular Dynamics of Fibrinogen Adsorption onto Graphene, but Not onto Poly(ethylene glycol) Surface, Increases Exposure of Recognition Sites That Trigger Immune Response
journal contribution
posted on 2016-03-11, 00:00 authored by Nadiya Dragneva, Oleg Rubel, Wely B. FlorianoChanges
in the conformation of blood proteins due to their binding
to nonbiological surfaces is the initial step in the chain of immunological
reactions to foreign bodies. Despite the large number of experimental
studies that have been performed on fibrinogen adsorption to nonbiological
surfaces, a clear picture describing this complex process has eluded
researchers to date. Developing a better understanding of the behavior
of bioactive fibrinogen motifs upon their interaction with surfaces
may facilitate the design of advanced materials with improved biocompatibility.
This is especially important within the context of medical implants.
Here we present results of explicit-solvent, all-atom MD simulations
of the adsorption of the fibrinogen D-domain onto a graphene surface
and a poly(ethylene glycol) (PEG) surface. Our results are consistent
with experimental observations that interactions with PEG do not induce
significant conformational changes on immune-reactive sites present
in the D-domain of fibrinogen. In contrast, our results indicate that
significant conformational changes induced by adsorption to graphene
surfaces may occur under conditions that promote a high density of
blood proteins on the surface. The structural rearrangements observed
on graphene directly affect the secondary structure content of the
D-domain, with consequent exposure of the recognition sites P1 (γ190–202)
and P2 (γ377–395) and the subsite P2-C (γ383–395)
involved in immune response. Analysis of the structural parameters
of the MD conformers was shown to accurately assess the biocompatibility
of the modeled surfaces.