“…Our choice to focus on lipid bilayer systems is motivated by recent explorations of the uptake and accumulation of various engineered nanomaterials, typically composed of redox-inactive cores, by prokaryotic and eukaryotic cells, as well as their interaction with model cell membranes. − In particular, nanoparticle–phospholipid bilayer interactions have been investigated through a host of analytical techniques, including fluorescence spectroscopy, electrochemical impedance spectroscopy, quartz crystal microbalance with dissipation monitoring (QCM-D), and scanning probes. − However, these methods require tagged or labeled molecules, lack inherent surface sensitivity, or are not chemically specific. In contrast to these methods, vibrational sum-frequency generation (SFG) spectroscopy is applicable to study the various oscillators and determine structural and orientational information about them, directly at aqueous/solid interfaces with surface specificity. − SFG has been shown to provide structural and orientational information on supported lipid bilayer (SLB) interfaces in aqueous environments. ,− SFG has also been used to probe phase transitions of lipid bilayers, , kinetics of transbilayer movement of lipids, − bilayer asymmetry, and protein–lipid interactions. ,− The technique is particularly powerful when applied in conjunction with complementary methods when probing nanoparticle–membrane interactions, as we recently showed for gold metal nanoparticle–membrane interactions …”