Proteins are the machinery of life ­and understanding their structure provides important clues about their mode of action. Since proteins are so important for biology and medicine, more than 100.000 protein structures have been determined experimentally and are available in databases. At the same time, structural details about proteins bound to interfaces is extremely sparse – not a single structure of an interfacial protein can be found in the databases! And yet, much of biology takes place at interfaces such as membranes and biominerals. Another important current research are is the health impact of artifical biomaterials and the toxicity of microplastic. Sensor or nanotechnology application also often involve protein binding to surfaces. The current lack of information is, in part, explained by the experimental difficulty of determining a structure within a monomolecular protein layer in the overwhelming  presence of unbound proteins in solution near the interface. Here, sum frequency generation (SFG) spectroscopy has seen a small revolution in the last years and has been extended into a surface sensitive tool to probe protein structure in detail. We have recently developed methods combining molecular dynamics (MD) simulations with experimental and theoretical SFG spectroscopy to follow the binding, structure and motion of interfacial proteins, both on flat surfaces and nanoparticle interfaces. As recent examples, I will discuss breakthroughs in understanding how the formation of neurotoxic aggregates of α-synuclein, the protein implicated with Parkinson’s disease, is accelerated at cell membrane. Our data show that at slightly elevated concentrations, α-synuclein assumes a binding pose that promotes lateral aggregation at membrane interfaces. On nanoparticle surfaces, these interfacial effects are even more pronounced – which can be important for health in view of the large amounts of plastic particles we are exposed to every day. Investigating a number of human proteins freuquently observed on nanoplastic materials, we find that nanoparticles affect the conformation of human proteins much more than flat surfaces, an indication that the toxicity of plastics particles may currently be underestimated.