Cytochrome c Facilitates Binding between Lipid Bilayers and Citrate-Coated Gold Nanoparticles in Coarse-Grained Simulations.

Characterization and prediction of the interactions between engineered nanoparticles (ENPs), proteins, and biological membranes is critical for advancing applications to nanomedicine and nanomanufacturing while mitigating nanotoxicological risks. In this work, we employ a coarse-grained dissipative particle dynamics (DPD) simulation to investigate the interactions among cytochrome c (CytC), lipid bilayers, and citrate-coated gold nanoparticles (AuNPs). We updated the DPD potential to accurately represent binding potentials between molecules, and validated the model relative to an all-atom representation. The DPD simulations successfully replicate experimental observations: CytC facilitates the binding of citrate-coated AuNPs to lipid bilayers composed of 90% dioleoylphosphatidylcholine (DOPC) mixed with 10% stearoylphosphatidylinositol (SAPI) or 10% tetraoleoyl cardiolipin (TOCL) but not to pure 100% DOPC bilayers. In addition, the simulations reveal nuanced differences in binding preferences between CytC, the lipid bilayers, and the ENP, at a scale that is not presently directly observable in experiments. Specifically, we found that the surface coating of the nanoparticles─viz variations in the CytC surface density─affects the protein-mediated binding with the bilayers. Such a molecular-sensitive result underscores the utility of DPD simulations in simulating complex biological systems.