(662h) pH Driven Reorientation of Cytochrome c on Silica Nanoparticles: Effect of Surface Charge Distribution and Dipole Moment

In the past decade, nanoscience has found numerous biomedical applications, such as targeted molecular delivery, inâ??vivo imaging, sensing, and gene therapy. In almost all these applications, the active nanosized particles come in direct contact with biomolecular environments containing various proteins. Hence, developing a fundamental understanding on how proteins interact and self-assemble at nanoparticle surfaces is of eminent importance. Here we report an experimental study of the pH dependent spatial orientation of adsorbed cytochrome c onto silica nanoparticles (diameter 7 to 20 nm). We use small angle neutron scattering (SANS) to determine the equilibrium assembled state and spatial orientation of adsorbed cytochrome c in the pH range 2-11. We find that the protein orientation on nanoparticleâ??s surface is strongly correlated with its surface charge distribution and net dipole moment. Our comprehensive analysis of SANS data and protein surface charge distribution calculations indicates that the protein binds to the silica surface via its largest positive surface patch. This study provides a new way of analyzing and understanding protein-nanoparticle interactions, which may further contribute to the development of new approaches for fabricating surface-engineered materials for biomedical applications.