Virus-Sized Gold Nanorods: Plasmonic Particles for Biology.

Plasmons, collective oscillations of conduction-band electrons in nanoscale metals, are well-known phenomena in colloidal gold and silver nanocrystals that produce brilliant visible colors in these materials that depend on the nanocrystal size and shape. Under illumination at or near the plasmon bands, gold and silver nanocrystals exhibit properties that enable fascinating biological applications: (i) the nanocrystals elastically scatter light, providing a straightforward way to image them in complex aqueous environments; (ii) the nanocrystals produce local electric fields that enable various surface-enhanced spectroscopies for sensing, molecular diagnostics, and boosting of bound fluorophore performance; (iii) the nanocrystals produce heat, which can lead to chemical transformations at or near the nanocrystal surface and can photothermally destroy nearby cells. While all the above-mentioned applications have already been well-demonstrated in the literature, this Account focuses on several other aspects of these nanomaterials, in particular gold nanorods that are approximately the size of viruses (diameters of ∼10 nm, lengths up to 100 nm). Absolute extinction, scattering, and absorption properties are compared for gold nanorods of various absolute dimensions, and references for how to synthesize gold nanorods with four different absolute dimensions are provided. Surface chemistry strategies for coating nanocrystals with smooth or rough shells are detailed; specific examples include mesoporous silica and metal-organic framework shells for porous (rough) coatings and polyelectrolyte layer-by-layer wrapping for "smooth" shells. For self-assembled-monolayer molecular coating ligands, the smoothest shells of all, a wide range of ligand densities have been reported from many experiments, yielding values from less than 1 to nearly 10 molecules/nm2 depending on the nanocrystal size and the nature of the ligand. Systematic studies of ligand density for one particular ligand with a bulky headgroup are highlighted, showing that the highest ligand density occurs for the smallest nanocrystals, even though these ligand headgroups are the most mobile as judged by NMR relaxation studies. Biomolecular coronas form around spherical and rod-shaped nanocrystals upon immersion into biological fluids; these proteins and lipids can be quantified, and their degree of adsorption depends on the nanocrystal surface chemistry as well as the biophysical characteristics of the adsorbing biomolecule. Photothermal adsorption and desorption of proteins on nanocrystals depend on the enthalpy of protein-nanocrystal surface interactions, leading to light-triggered alteration in protein concentrations near the nanocrystals. At the cellular scale, gold nanocrystals exert genetic changes at the mRNA level, with a variety of likely mechanisms that include alteration of local biomolecular concentration gradients, changes in mechanical properties of the extracellular matrix, and physical interruption of key cellular processes-even without plasmonic effects. Microbiomes, both organismal and environmental, are the likely first point of contact of nanomaterials with natural living systems; we see a major scientific frontier in understanding, predicting, and controlling microbe-nanocrystal interactions, which may be augmented by plasmonic effects.

Biologically Representative Lipid-Coated Gold Nanoparticles and Phospholipid Vesicles for the Study of Alpha-Synuclein/Membrane Interactions.

Alpha-synuclein is an intrinsically disordered protein whose formation of beta-sheet-rich protein aggregates in the brain is implicated in the development of Parkinson's disease. Due to its believed role in synaptic vesicle trafficking and neurotransmission, many studies have employed simple, synthetic model systems to investigate alpha-synuclein/membrane interactions in an attempt to gain a better understanding of the protein's native and pathogenic functions. Interestingly, these studies seem to suggest that alpha-synuclein interacts differently with rigid vesicle mimics in comparison to malleable vesicle mimics. However, the use of different mimic sizes and surface chemistries across existing studies makes it challenging to directly compare the effects of membrane mechanical properties on protein behavior observed thus far. In this work, we developed a synaptic vesicle mimic library comprising a range of both malleable and rigid synaptic vesicle mimics possessing the same size and biologically representative lipid surface chemistry. Limited proteolysis mass spectrometry experiments revealed distinct fragmentation patterns between rigid and malleable synaptic vesicle mimics. The N-terminal and C-terminal regions of alpha-synuclein were found to become less solvent-accessible upon binding to all synaptic vesicle mimics. Nevertheless, minor variations in digestion pattern were observed in the central region of the protein dependent upon mimic size, rigidity, and lipid composition. Higher binding affinities were observed for alpha-synuclein binding to rigid synaptic vesicle mimics compared to malleable synaptic vesicle mimics. Additionally, the binding affinity of alpha-synuclein toward small lipid vesicles and small lipid-coated gold nanoparticles without cholesterol was found to be lower than that of their respective malleable and rigid counterparts. Interestingly, the binding curves for the rigid synaptic vesicle mimics demonstrated a nontraditional peak and dip shape believed to arise from differences in alpha-synuclein orientation on the particle surface at different protein-to-particle incubation ratios.

Site-selective modification of metallic nanoparticles.

Surface patterning of inorganic nanoparticles through site-selective functionalization with mixed-ligand shells or additional inorganic material is an intriguing approach to developing tailored nanomaterials with potentially novel and/or multifunctional properties. The unique physicochemical properties of such nanoparticles are likely to impact their behavior and functionality in biological environments, catalytic systems, and electronics applications, making it vital to understand how we can achieve and characterize such regioselective surface functionalization. This Feature Article will review methods by which chemists have selectively modified the surface of colloidal nanoparticles to obtain both two-sided Janus particles and nanoparticles with patchy or stripey mixed-ligand shells, as well as to achieve directed growth of mesoporous oxide materials and metals onto existing nanoparticle templates in a spatially and compositionally controlled manner. The advantages and drawbacks of various techniques used to characterize the regiospecificity of anisotropic surface coatings are discussed, as well as areas for improvement, and future directions for this field.

Interaction of Alpha-Synuclein and Its Mutants with Rigid Lipid Vesicle Mimics of Varying Surface Curvature.

Abnormal aggregation of alpha-synuclein (α-syn), an intrinsically disordered neuronal protein, is strongly implicated in the development of Parkinson's disease. Efforts to better understand α-syn's native function and its pathogenic role in neurodegeneration have revealed that the protein interacts with anionic lipid vesicles via adoption of an amphipathic α-helical structure; however, the ability of α-syn to remodel lipid membranes has made it difficult to decipher the role of vesicle surface curvature in protein binding behavior. In this study, sodium dodecyl sulfate (SDS)-coated gold nanoparticles (AuNPs), which mimic bilayer vesicle architecture, were synthesized in order to conduct a systematic investigation into the binding interaction of α-syn and two of its mutants (A30P and E46K) with rigid lipid vesicle mimics of defined surface curvature. By incorporating a rigid AuNP core (∼10-100 nm), the ability of α-syn to remodel the vesicle mimics was removed and their surface curvature could be fixed. Proteomics studies showed that, upon binding of free α-syn to the surface of SDS-AuNPs, the N-terminus of α-syn became less solvent accessible, whereas its C-terminus became more accessible. Interestingly, α-syn's non-amyloid-ß component (NAC) region also exhibited increased solvent accessibility, suggesting that α-syn bound to rigid vesicle-like structures could possess heightened aggregation propensity and therefore pathogenicity. Additionally, both the A30P and E46K mutations were found to adopt distinct binding modes on the mimics' surface. In contrast with previous reports, similar binding affinities were observed for WT, A30P, and E46K α-syn toward SDS-AuNPs of all sizes, indicating the potential importance of vesicle deformability in determining α-syn binding behavior.

Seed-mediated co-reduction in a large lattice mismatch system: synthesis of Pd-Cu nanostructures.

Metal nanoparticles (NPs) are of interest for applications in catalysis, electronics, chemical sensing, and more. Their utility is dictated by their composition and physical parameters such as particle size, particle shape, and overall architecture (e.g., hollow vs. solid). Interestingly, the addition of a second metal to create bimetallic NPs adds multifunctionality, with new emergent properties common. However, synthesizing structurally defined bimetallic NPs remains a great challenge. One synthetic pathway to architecturally controlled bimetallic NPs is seed-mediated co-reduction (SMCR) in which two metal precursors are simultaneously co-reduced to deposit metal onto shape-controlled metal seeds, which direct the overgrowth. Previously demonstrated in a Au-Pd system, here SMCR is applied to a system with a larger lattice mismatch between the depositing metals: Pd and Cu (7% mismatch for Pd-Cu vs. 4% for Au-Pd). Through manipulation of precursor reduction kinetics, the morphology and bimetallic distribution of the resultant NPs can be tuned to achieve eight-branched Pd-Cu heterostructures with Cu localized at the tips of the Pd nanocubes as well as branched Pd-Cu alloyed nanostructures and polyhedra. Significantly, the symmetry of the seeds can be transferred to the final nanostructures. This study expands our understanding of SMCR as a route to structurally defined bimetallic nanostructures and the synthesis of multicomponent nanomaterials more generally.