Biophysical characterization of nanoparticle-endothelial model cell membrane interactions.

Understanding the biophysical interactions of nanoparticles (NPs) with cell membranes is critical for developing effective nanocarrier systems for drug delivery applications. We developed an endothelial model cell membrane (EMM) using a mixture of lipids and Langmuir balance to study its interaction with NPs. Polystyrene NPs of different surface chemistry and sizes were used as a model nanomaterial, and changes in the membrane's surface pressure (SP) were used as a parameter to monitor its interactions with NPs. Aminated NPs (60 nm) increased SP, plain NPs reduced it, and carboxylated NPs of the same size had no effect. However, smaller NPs (20 nm) increased SP irrespective of surface chemistry, and serum did not influence their SP effect, whereas it masked the effect of larger (>60 nm) plain and carboxylated but not that of aminated NPs. Membranes formed with a single phospholipid showed a different pattern of interactions with NPs than that with EMM, signifying the need of using a mixture of lipids representing the respective cells/tissue of interest for a model membrane. The particular effect of NP characteristics on SP, determined using atomic force microscopy and pi- A (surface pressure-area) isotherm, can be explained on the basis of whether the interaction results in condensation of phospholipids (increase in SP) or their displacement from the interface into the subphase (decrease in SP), causing destabilization of the membrane. We conclude that NP characteristics significantly influence biophysical interactions with the membrane. Further, the molecular mechanism(s) of nanoparticle interactions with model membranes can be effectively used for optimizing the characteristics of nanomaterials for particular biological applications.