Size dependence of gold nanoparticle interactions with a supported lipid bilayer: A QCM-D study

Abstract Knowledge of nanoparticle (NP)–membrane interactions is important to advances in nanomedicine as well as for determining the safety of NPs to humans and the ecosystem. This study focuses on a unique mechanism of cytotoxicity, cell membrane destabilization, which is principally dependent on the nanoparticle nature of the material rather than on its molecular properties. We investigated the interactions of 2, 5, 10, and 40 nm gold NPs with supported lipid bilayer (SLB) of L-α-phosphatidylcholine using quartz crystal microbalance with dissipation monitoring (QCM-D). Gold NPs were tested both in the absence of and in the presence of polymethacrylic acid (PMAA), used to simulate the natural organic matter (NOM) in the environment. In the absence of PMAA, for all NP sizes, we observed only small mass losses (1 to 6 ng) from the membrane. This small lipid removal may be a free energy lowering mechanism to relieve stresses induced by the adsorption of NPs, with the changes too small to affect the membrane integrity. In the presence of PMAA, we observed a net mass increase in the case of smaller NPs. We suggest that the increased adhesion between the NP and the bilayer, promoted by PMAA, causes sufficient NP adsorption on the bilayer to overcompensate for any loss of lipid. The most remarkable observation is the significant mass loss (60 ng) for the case of 40 nm NPs. We attribute this to the lipid bilayer engulfing the NP and leaving the crystal surface. We propose a simple phenomenological model to describe the competition between the particle-bilayer adhesion energy, the bilayer bending energy, and the interfacial energy at bilayer defect edges. The model shows that the larger NPs, which become more adhesive because of the polymer adsorption, are engulfed by the bilayer and leave the crystal surface, causing large mass loss and membrane disruption. The QCM-D measurements thus offer direct evidence that even if NPs are intrinsically not cytotoxic, they can become cytotoxic in the presence of environmental organic matter which modulates the adhesive interactions between the nanoparticle and the membrane.