Due to their well-defined surface chemistry, nanoparticles (NPs) are of great interest, having found numerous biological applications, such as biosensing, bioimaging, and drug delivery. When NPs are exposed to biological fluids, the proteins in solution will compete to bind to the NP surface. However, it remains impossible to predict the competitive binding outcome of proteins to NPs, knowledge that would be useful for scientists wanting to target NPs to specific cells in the body. Here, NMR methods were used to investigate how proteins compete to bind to various NP surfaces, as well as to explore aspects of kinetic and thermodynamic control. Specifically, we use a 1H-15N HSQC technique to quantify AuNP binding for various mixtures of GB3 and Ubiquitin, two small model proteins, as well as Amidase and R2ab, two larger protein domains from S. epidermidis implicated in biofilm formation. Using CPMG relaxation experiments, we monitored the timescale of protein exchange with a pretreated, protein functionalized AuNP surface, as well as the protein exchange with SiNP surface. The AuNP surface was found to have a hard corona with no observable difference in the relaxation rates. However, SiNPs exhibit a soft corona with a measurable protein dynamics (ΔR2). Since the proteins harden quickly on AuNP surfaces, the mixtures were sampled at 1.5 h intervals to investigate and quantify the protein competition binding over time. Our results suggest that the competition is not kinetically controlled, but thermodynamically controlled as the competition between proteins leads to an increased surface exchange rate (~ms). This differs slightly from a previous study, where surface exchange was extremely slow (18 h). Together, our results suggest a mechanism by which NP surface character may change over time, and this may be an important consideration in the design of NP-based therapeutics.

Investigating thermodynamics and kinetic control mechanism for competitive protein adsorption to a nanoparticle surface

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.