Systematic probing of protein adsorption on protein-based nanoparticles in dependence of the particle surface charge.

Understanding protein adsorption on the surface of nanoparticles (NPs) is crucial for determining their behavior in biological environments. Early research in this field faced challenges in producing high-quality NPs. Advancements in NP fabrication now allow for precise modifications of specific parameters, such as zeta potential. However, creating a series of NPs where only one parameter, such as surface charge, is independently varied remains challenging due to concurrent alterations in other properties. In this study, we address these challenges using the ferritin nanocage (Ftn) as a model system for NPs. By modifying only a few amino acids on the outer surface of Ftn, we produce NPs with highly defined properties, focusing solely on variations in surface charge. This approach enables us to generate a controlled series of protein-based nanocages, labeled with fluorophores inside the nanocage. We utilize fluorescent correlation spectroscopy (FCS) to investigate the adsorption of bovine serum albumin (BSA) on these NPs, analyzing the dependence of BSA binding on surface charge. This fundamental study enhances our understanding of the driving forces behind protein adsorption, contributing valuable insights into the design of NPs for biomedical applications.