Molecular Dynamics of Fibrinogen Adsorption onto Graphene, but Not onto Poly(ethylene glycol) Surface, Increases Exposure of Recognition Sites That Trigger Immune Response.

Changes 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.

Binding of solvated peptide (EPLQLKM) with a graphene sheet via simulated coarse-grained approach.

Binding of a solvated peptide A1 ((1)E (2)P (3)L (4)Q (5)L (6)K (7)M) with a graphene sheet is studied by a coarse-grained computer simulation involving input from three independent simulated interaction potentials in hierarchy. A number of local and global physical quantities such as energy, mobility, and binding profiles and radius of gyration of peptides are examined as a function of temperature (T). Quantitative differences (e.g., the extent of binding within a temperature range) and qualitative similarities are observed in results from three simulated potentials. Differences in variations of both local and global physical quantities suggest a need for such analysis with multiple inputs in assessing the reliability of both quantitative and qualitative observations. While all three potentials indicate binding at low T and unbinding at high T, the extent of binding of peptide with the temperature differs. Unlike un-solvated peptides (with little variation in binding among residues), solvation accentuates the differences in residue binding. As a result the binding of solvated peptide at low temperatures is found to be anchored by three residues, (1)E, (4)Q, and (6)K (different from that with the un-solvated peptide). Binding to unbinding transition can be described by the variation of the transverse (with respect to graphene sheet) component of the radius of gyration of the peptide (a potential order parameter) as a function of temperature.