The effect of nanoscale surface curvature on the oligomerization of surface-bound proteins

Abstract

ReviewCite this article: Kurylowicz M, Paulin H, Mogyoros J, Giuliani M, Dutcher JR. 2014 The effect of nanoscale surface curvature on the oligomerization of surface-bound proteins. J. R. Soc. The influence of surface topography on protein conformation and association is used routinely in biological cells to orchestrate and coordinate biomolecular events. In the laboratory, controlling the surface curvature at the nanoscale offers new possibilities for manipulating protein-protein interactions and protein function at surfaces. We have studied the effect of surface curvature on the association of two proteins, a-lactalbumin (a-LA) and b-lactoglobulin (b-LG), which perform their function at the oil-water interface in milk emulsions. To control the surface curvature at the nanoscale, we have used a combination of polystyrene (PS) nanoparticles (NPs) and ultrathin PS films to fabricate chemically pure, hydrophobic surfaces that are highly curved and are stable in aqueous buffer. We have used single-molecule force spectroscopy to measure the contour lengths L c for a-LA and b-LG adsorbed on highly curved PS surfaces (NP diameters of 27 and 50 nm, capped with a 10 nm thick PS film), and we have compared these values in situ with those measured for the same proteins adsorbed onto flat PS surfaces in the same samples. The L c distributions for b-LG adsorbed onto a flat PS surface contain monomer and dimer peaks at 60 and 120 nm, respectively, while a-LA contains a large monomer peak near 50 nm and a dimer peak at 100 nm, with a tail extending out to 200 nm, corresponding to higher order oligomers, e.g. trimers and tetramers. When b-LG or a-LA is adsorbed onto the most highly curved surfaces, both monomer peaks are shifted to much smaller values of L c . Furthermore, for b-LG, the dimer peak is strongly suppressed on the highly curved surface, whereas for a-LA the trimer and tetramer tail is suppressed with no significant change in the dimer peak. For both proteins, the number of higher order oligomers is significantly reduced as the curvature of the underlying surface is increased. These results suggest that the surface curvature provides a new method of manipulating protein-protein interactions and controlling the association of adsorbed proteins, with applications to the development of novel biosensors.

Organic Nanoflowers from a Wide Variety of Molecules Templated by a Hierarchical Supramolecular Scaffold

“…36 The topography and curvature on the particle surface may also play a role in determining the interactions of the adsorbed guests as reported for other particle–protein systems (e.g., albumin, fibrinogen). 35,38 …”

Superhydrophobic materials for biomedical applications

“…When the surfaces are under high shear, less protein adsorption occurs. Further, Kurylowicz et al [135] showed that as surface curvature increased, the number of protein dimers and higher order aggregates decreased. The authors use polystyrene (PS) surfaces, either flat or with adsorbed nanoparticles that are 50 or 27 nm in diameter, and employ single-molecule force microscopy to show that lactalbumin and lactoglobulin are more closely packed on the flat than highly curved surfaces.…”

Understanding and exploiting nanoparticles' intimacy with the blood vessel and blood

“…167 As the surface curvature (k) of a sphere can be defined simply as a reciprocal to the radius (R), k = 1/R, 177 a decrease in particle size would therefore translate to a significant increase in the local curvature. 179 Along the same line, the manner in which the proteins adsorb, arrange and pack on the nanomaterials surface will therefore be highly dependent on the nanomaterials surface curvature. 178 When a protein approaches a NM with a diameter that is so much bigger than the size of the protein, what the protein 'perceives' is essentially a flat surface.…”