Soft Interactions at Nanoparticles Alter Protein Function and Conformation in a Size Dependent Manner

Abstract

Weak protein-nanoparticle (NP) interactions are studied in a low binding regime as a model for the soft protein corona around nanoparticles in complex biological fluids. Noncovalent, reversible interactions between Subtilisin Carlsberg (SC) and silica NPs shows significant alteration in conformation and enzymatic activity in a NP-size dependent manner. Very weak interactions between SC and silica NPs were revealed by centrifugation-based separations and further supported by small-angle X-ray scattering, while bovine serum albumin was used as a strongly interacting reference. Secondary and tertiary structure changes of SC were studied via circular dichroism and correlated to enzymatic activity where the enzyme kinetics showed a critical role for nanoparticle size.

Analysis of zinc oxide nanoparticles binding proteins in rat blood and brain homogenate

“…Even weak interactions between protein and ZnO NPs may result in conformational and functional changes in a size-dependent manner. 37 These results support the theory that absorb bound proteins onto the surface of NPs may undergo conformational change, potentially developing reversible and irreversible configurations.…”

Biomolecular coronas provide the biological identity of nanosized materials

“…This highlights the fact that biological impacts might be driven by both the composition of the biomolecular corona and disturbances to the conformation of the proteins following adsorption on the nanoparticles 10, [67][68][69][70][71][72] . One example where the mechanism has been worked out involves the nanoparticle-induced protein unfolding leading to initiation of the NF-Kβ pathway and inflammation For example, endocytosis of nanoparticles across the plasma membrane occurs within minutes 46,50 , and, consequently, a biomolecule must stay on the nanoparticle surface at least this long in order to be 'seen' and processed by the endocytic machinery.…”

“…The hard corona structure can also be studied by isolating the particle-corona , surface plasmon resonance 32,86,92 , small angle X-ray scattering 67,91,93 , quartz crystal microbalance 94 , isothermal titration calorimetry 86,93,95 , UV-vis and fluorescence spectroscopies 68,96 . Adsorption on the nanoparticle surface may result in protein conformational changes, and these have been studied by circular dichroism 6, 67,68,72,80 , infrared spectroscopy 69,80 , NMR 85,97 , and enzyme activity assays 67,68,98 .…”

“…Adsorption on the nanoparticle surface may result in protein conformational changes, and these have been studied by circular dichroism 6, 67,68,72,80 , infrared spectroscopy 69,80 , NMR 85,97 , and enzyme activity assays 67,68,98 . Morphological analysis of the corona-nanoparticle complexes has been carried out using transmission electron microscopy and atomic force microscopy 6,67 and emerging computational studies seek to correlate with experimental results 6, [99][100][101] .…”

Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface

“…In some cases this seems successful, 3 but in others less so (for example targeting moieties can hinder biological barrier penetration 8,11 ). Practical problems include the fact that surface-grafting of biofunctional moieties may disrupt protein structure and function 21,22 , or constrain its orientation.…”