The interaction of β2-microglobulin and gold nanoparticles: impact of coating, charge and size

Gold nanoparticles (AuNPs) proved to be ideal scaffolds to build nanodevices whose performance can be tuned by changing their coating. In particular, their interaction with proteins revealed to be highly dependent on the physico-chemical properties of the gold cluster protecting monolayer. In this work we studied the behavior of three different alkanethiolate-coated AuNPs (AT-AuNPs) when they are incubated with a model amyloidogenic protein, β2-microglobulin (β2m), whose clinical relevance in dialysis-related amyloidosis (DRA) and structural properties are well known. To this aim we synthesized 6-mercaptohexanoic acid-coated AuNPs (MHA-AuNPs) and (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-coated AuNPs (MUTAB-AuNPs) of 7.5 nm diameter and 3-mercaptopropionic acid-coated AuNPs (MPA-AuNPs) of 3.6 nm diameter. To study the effects of the incubation with β2m of these NPs that differ in charge and dimension, we employed NMR, UV-Vis and fluorescence spectroscopy, along with transmission electron microscopy (TEM). The three tested AuNP systems gave different results. We found that MHA-AuNPs precipitate with the protein into large agglomerates inducing β2m unfolding, MUTAB-AuNPs precipitation is triggered by the protein that remains unchanged in solution, at least at the higher considered protein/NP ratio, and MPA-AuNPs interact preferentially with a localized region of the protein that stays essentially stably dissolved. These results stress the complexity of the bio-nano interface and the relevance and viability of a fine control of NP properties to master protein-NP interactions.