Noncovalent protein-nanoparticle(NP) interactions are of utmost interest in several fields of nanoscience, including nanomedicine, toxicology, and sensing. Protein adsorption influences NP bioreactivity, and controlled protein-NP interactions can be exploited for the development of hybrid devices and artificial receptors. An in-depth description of nano-bio interfaces constitutes an essential step towards the formulation of predictive structure-activity relationships.
Transient protein-NP interactions have been recently demonstrated to be accessible by solution NMR spectroscopy. These developments offer tremendous opportunities for an improved understanding of adsorption mechanisms. However, the complexity and variety of protein-NP systems present significant challenges and urge improved methods for a more extensive description of adsorption processes.
Here, we aim at a detailed investigation of representative protein-NP interactions by use of protein-observed NMR experiments in combination with software programs for analysis of experimental data. Indeed, residue-resolved spectra are information rich, reporting on contact sites, structural rearrangements, dynamics, kinetics and thermodynamics of the interactions. We will use lineshape simulations, chemical shift perturbation mapping, and perturbation covariance analysis to rationalize binding-dependent spectral changes and establish correlations between adsorption mechanisms and physicochemical properties of interacting partners.
We will focus on lipid nanovesicles as a highly versatile nanoparticle platform, and on three model protein systems displaying distinct structural and chemical properties: the globular ubiquitin, the partly flexible UIM domain, and the intrinsically disordered Tau.
We expect that the proposed project will provide new fundamental insights into nano-bio interactions, supporting applications of NPs in biosciences.