(67a) Interactions of Engineered Nanomaterials with the Cell Plasma Membrane

Most biomedical applications of nanotechnology require that engineered nanomaterials come into direct contact with mammalian cells. The cell plasma membrane, a lipid bilayer surrounding all cells, is the first cellular entity that interacts with incoming nanomaterials. Depending on dose, and nanoparticle and membrane properties, engineered nanomaterials are capable of disrupting the cell membrane, thereby causing cell toxicity. Due to the complex structure of the cell membrane, mechanistic research on nanoparticle-membrane interactions has primarily relied on membrane models. However, while a variety of nanoparticle properties have been examined, the structural complexities of the plasma membrane such as the compositional asymmetry of membrane leaflets and the presence of membrane domains have been overlooked. This has led to a lack of understanding on the mechanisms of nanoparticle-induced cell membrane damage. In this talk, I will discuss efforts in my group to develop membrane models that capture the complexities of the cell membrane and use these models to uncover the mechanisms by which nanomaterials disrupt membrane structure and integrity. These efforts demonstrate the important role of nanoparticle physicochemical properties and biomolecular corona, as well as membrane composition and biophysical properties in regulating nanoparticle-induced membrane damage. I will also provide an overview on our work on going beyond simple membrane models and utilizing live cells as the “model” to probe nanoparticle-membrane interactions.