No abstract

Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular, and protein levels due to their unusual physicochemical properties (e.g., small size, high surface area to volume ratio, chemical composition, crystallinity, electronic properties, surface structure reactivity and functional groups, inorganic or organic coatings, solubility, shape, and aggregation behavior). Metal NPs, in particular, have received increasing interest due to their widespread medical, consumer, industrial, and military applications. However, as particle size decreases, some metal-based NPs are showing increased toxicity, even if the same material is relatively inert in its bulk form (e.g., Ag, Au, and Cu). NPs also interact with proteins and enzymes within mammalian cells and they can interfere with the antioxidant defense mechanism leading to reactive oxygen species generation, the initiation of an inflammatory response and perturbation and destruction of the mitochondria causing apoptosis or necrosis. As a result, there are many challenges to overcome before we can determine if the benefits outweigh the risks associated with NPs.

Proteins show diverse responses when placed under mechanical stress. The molecular origins of their differing mechanical resistance are still unclear, although the orientation of secondary structural elements relative to the applied force vector is thought to have an important function. Here, by using a method of protein immobilization that allows force to be applied to the same all-beta protein, E2lip3, in two different directions, we show that the energy landscape for mechanical unfolding is markedly anisotropic. These results, in combination with molecular dynamics (MD) simulations, reveal that the unfolding pathway depends on the pulling geometry and is associated with unfolding forces that differ by an order of magnitude. Thus, the mechanical resistance of a protein is not dictated solely by amino acid sequence, topology or unfolding rate constant, but depends critically on the direction of the applied extension.

We report the light-to-heat energy transfer efficiencies of gold nanoparticles with variable sizes by assessing the temperature profiles of laser-activated particle suspensions in water. Gold nanoparticles with sizes ranging from 5 to 50 nm were synthesized by chemical reduction methods using sodium borohydride, sodium citrate, or hydroquinone as reducing agents. As-synthesized gold nanoparticle solution (1 mL) was loaded into a quartz cuvette and exposed to a CW green laser (532 nm). Heat input into the system by energy transfer from nanoparticles equals heat dissipation at thermal equilibrium. The transducing efficiency was then determined by plotting temperature increase as a function of laser power extinction. The efficiency increases from 0.650 ± 0.012 to 0.803 ± 0.008 as the particle size decreases from 50.09 ± 2.34 to 4.98 ± 0.59 nm, respectively. The results indicate that the photothermal properties of gold nanoparticles are size-tunable, and the variation of efficiency can be correlated to the absorption/extinction ratios calculated by Mie theory for different particle sizes. We further expanded our Mie theory calculations of absorption/extinction ratios to a broader range of diameters and wavelengths. These studies are crucial for practical applications of gold nanoparticles in nanotechnology and bioengineering, such as enhancing the treatment efficiency of laser surgery.

beta-sheet proteins are generally more able to resist mechanical deformation than alpha-helical proteins. Experiments measuring the mechanical resistance of beta-sheet proteins extended by their termini led to the hypothesis that parallel, directly hydrogen-bonded terminal beta-strands provide the greatest mechanical strength. Here we test this hypothesis by measuring the mechanical properties of protein L, a domain with a topology predicted to be mechanically strong, but with no known mechanical function. A pentamer of this small, topologically simple protein is resistant to mechanical deformation over a wide range of extension rates. Molecular dynamics simulations show the energy landscape for protein L is highly restricted for mechanical unfolding and that this protein unfolds by the shearing apart of two structural units in a mechanism similar to that proposed for ubiquitin, which belongs to the same structural class as protein L, but unfolds at a significantly higher force. These data suggest that the mechanism of mechanical unfolding is conserved in proteins within the same fold family and demonstrate that although the topology and presence of a hydrogen-bonded clamp are of central importance in determining mechanical strength, hydrophobic interactions also play an important role in modulating the mechanical resistance of these similar proteins.