Protein Interactions with Nanoparticle Surfaces: Highlighting Solution NMR Techniques.

In the last decade, nanoparticles (NPs) have become a key tool in medicine and biotechnology as drug delivery systems, biosensors and diagnostic devices. The composition and surface chemistry of NPs vary based on the materials used: typically organic polymers, inorganic materials, or lipids. Nanoparticle classes can be further divided into sub-categories depending on the surface modification and functionalization. These surface properties matter when NPs are introduced into a physiological environment, as they will influence how nucleic acids, lipids, and proteins will interact with the NP surface. While small-molecule interactions are easily probed using NMR spectroscopy, studying protein-NP interactions using NMR introduces several challenges. For example, globular proteins may have a perturbed conformation when attached to a foreign surface, and the size of NP-protein conjugates can lead to excessive line broadening. Many of these challenges have been addressed, and NMR spectroscopy is becoming a mature technique for analysis of NP binding behavior. It is therefore not surprising that NMR has been applied to NP systems and has been used to study biomolecules on NP surfaces. Important considerations include corona composition, protein behavior, and ligand architecture. These features are difficult to resolve using classical surface and material characterization strategies, and NMR provides a complementary avenue of characterization. In this review, we examine how solution NMR can be combined with other analytical techniques to investigate protein behavior on NP surfaces.