(338b) Human Serum Protein Corona Greatly Changes the Interactions between Nanoparticles and a Model Human Erythrocyte (RBC) Membrane

Proteins in physiological fluids rapidly bind to nanoparticles (NPs), forming a protein corona (PC) that ultimately determines the biological identity of a nanoparticle. It is generally believed that the protein corona is responsible for controlling the colloidal stability of NPs, the way in which NPs taken up by cells and how NPs biodistribute and lead to toxicity. Investigating NPs interactions with cell membranes is a critical first step to understanding the extent of biological destabilization when NPs contact cells. This work describes the use of dynamic surface pressure measurements, coupled with fluorescence microscopy to investigate how the NP-cell membrane interactions are modulated by the presence of a protein (human serum albumin), either free in the environment or included in hard and/or soft coronas. Lipid monolayers are formed by depositing mixtures of phosphatidylcholine (PC), phosphoethanolamine (PE) and sphingomyelin (SM) at air-water interface to model a human erythrocyte (RBC) membranes outer leaflet. A suspension of polystyrene (PS) or protein−PS complexes is injected into the subphase, and dynamic changes in surface pressure (π) are monitored to evaluate the extent of NPs binding and the monolayer response. Our results show that PS NPs modify the monolayer phase behavior and cause lipid extraction and hole formation at high monolayer surface pressure (30 mN m^-1). Complexation of the PS NPs with proteins promotes their attachment to the lipid monolayers. PS NPs-hard corona (HC) complexes cause lipid extraction at high monolayer surface pressure (30 mN m^-1) and lead to the modification of the monolayer phase behavior with hindering of growth of solid domains. NPs-soft corona (SC) complexes, thus far not considered important for such interactions, induced greater changes in monolayer structure than the NPs alone at the same concentration. Compared to NP-HC complexes, NP-SC complexes yield more disordered structure in monolayers with less cohesion between the lipid molecules.