Neutron Reflectometry reveals the interaction between functionalized SPIONs and the surface of lipid bilayers

The safe application of nanotechnology devices in biomedicine requires fundamental understanding on how they interact with and affect the different components of biological systems. In this respect, the cellular membrane, the cell envelope, certainly represents an important target or barrier for nanosystems. Here we report on the interaction between functionalized SuperParamagnetic Iron Oxide Nanoparticles (SPIONs), promising contrast agents for Magnetic Resonance Imaging (MRI), and lipid bilayers that mimic the plasma membrane. Neutron Reflectometry, supported by Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) experiments, was used to characterize this interaction by varying both SPION coating and lipid bilayer composition. In particular, the interaction of two different SPIONs, functionalized with a cationic surfactant and a zwitterionic phospholipid, and lipid bilayers, containing different amount of cholesterol, were compared. The obtained results were further validated by Dynamic Light Scattering (DLS) measurements and Cryogenic Transmission Electron Microscopy (Cryo-TEM) images. None of the investigated functionalized SPIONs were found to disrupt the lipid membrane. However, in all case we observed the attachment of the functionalized SPIONs onto the surface of the bilayers, which was affected by the bilayer rigidity, i.e. the cholesterol concentration.