Transferrin (Tf) conjugated to gold nanoparticles and clusters combine the protein's site-specific receptor targeting capabilities with the optical properties imparted by the nano-sized gold. We have described two different synthesis protocols, one yielding fluorescent Tf-stabilized gold nanoclusters (AuNCs) and one yielding Tf-stabilized gold nanoparticles that exhibit localized surface plasmon resonance. We demonstrate that the synthetic route employed has a large influence both on the gold nanostructure formed, and also on the structural integrity of the protein. A slight protein unfolding allows stronger interaction with lipids, and was found to significantly perturb lipid monolayers. Interactions between the protein-gold nanostructures and three different cell types were also assessed, indicating that the enhanced membrane affinity may be attributed to intercellular membrane differences.