Effect of protein corona on nanoparticle-plasma membrane and nanoparticle-biomimetic membrane interactions

Nanomaterial contamination in the environment poses severe threats to public health and wellness. Understanding interactions between nanoparticles and biomembranes is pivotal to understanding the physiological effects of nanomaterials. The prevailing understanding is that a protein corona forms around nanoparticles upon their entering biological systems. The effect of the protein corona on the membrane–nanoparticle interaction has not been comprehensively investigated. Here, we report a systematic study to better understand the effects of the protein corona on nanoparticle–biomembrane interactions with both plasma membranes (293T cell line) and biomimetic membranes. Giant plasma membrane vesicles (GPMVs) and giant unilamellar vesicles (GUVs) fabricated from organ lipid extracts (brain, heart, and liver) served as biomimetic models in our study. Reduced charged-nanoparticle adhesion to both plasma and biomimetic membranes with the presence of the protein corona suggests that the protein corona interferes with the electrostatic interaction between nanoparticles and biomembranes. These similar trends of nanoparticle adhesion among the membranes indicated that model membranes can capture this electrostatic interaction with similar responses as plasma membranes. However, the membrane integrity subsequent to the interaction was different between the two systems, indicating the limitations of model membranes in recreating the complexity and dynamics of plasma membranes. As the first systematic study correlating nanoparticle interactions with cell membranes, isolated cell membranes, and synthetic vesicles from natural lipid extracts, we demonstrated that biomimetic membranes can serve as excellent analogues to cell membranes in providing fundamental insights regarding the electrostatic interaction between nanoparticles and biomembranes.