Photocontrollable Probe Spatiotemporally Induces Neurotoxic Fibrillar Aggregates and Impairs Nucleocytoplasmic Trafficking.

The abnormal assembly of misfolded proteins into neurotoxic aggregates is the hallmark associated with neurodegenerative diseases. Herein, we establish a photocontrollable platform to trigger amyloidogenesis to recapitulate the pathogenesis of amyotrophic lateral sclerosis (ALS) by applying a chemically engineered probe as a "switch" in live cells. This probe is composed of an amyloidogenic peptide from TDP-43, a photolabile linker, a polycationic sequence both to mask amyloidogenicity and for cell penetration, and a fluorophore for visualization. The photocontrollable probe can self-assemble into a spherical vesicle but rapidly develops massive nanofibrils with amyloid properties upon photoactivation. The photoinduced in vitro fibrillization process is characterized by biophysical techniques. In cellular experiments, this cell-penetrable vesicle was retained in the cytoplasm, seeded the mislocalized endogenous TDP-43 into aggregates upon irradiation, and consequently initiated apoptosis. In addition, this photocontrollable vesicle interfered with nucleocytoplasmic protein transport and triggered cortical neuron degeneration. Our developed strategy provides in vitro and in vivo spatiotemporal control of neurotoxic fibrillar aggregate formation, which can be readily applied in the studies of protein misfolding, aggregation-induced protein mislocalization, and amyloid-induced pathogenesis in different diseases.

Study of Binding Interaction between Pif80 Protein Fragment and Aragonite.

Pif is a crucial protein for the formation of the nacreous layer in Pinctada fucata. Three non-acidic peptide fragments of the aragonite-binding domain (Pif80) are selected, which contain multiple copies of the repeat sequence DDRK, to study the interaction between non-acidic peptides and aragonite. The polypeptides DDRKDDRKGGK (Pif80-11) and DDRKDDRKGGKDDRKDDRKGGK (Pif80-22) have similar binding affinity to aragonite. Solid-state NMR data indicate that the backbones of Pif80-11 and Pif80-22 peptides bound on aragonite adopt a random-coil conformation. Pif80-11 is a lot more effective than Pif80-22 in promoting the nucleation of aragonite on the substrate of ß-chitin. Our results suggest that the structural arrangement at a protein-mineral interface depends on the surface structure of the mineral substrate and the protein sequence. The side chains of the basic residues, which function as anchors to the aragonite surface, have uniform structures. The role of basic residues as anchors in protein-mineral interaction may play an important role in biomineralization.

Characterization and real-time imaging of the FTLD-related protein aggregation induced by amyloidogenic peptides.

We identify a new amyloidogenic peptide from the glutamine/asparagine-rich region of the FTLD-related protein (TDP-43), which can seed both the full-length and N-terminus-truncated TDP-43. Through the microinjection and real-time fluorescence imaging, we also found that this novel peptide could trigger cell apoptosis and initiate TDP-43 aggregation in the cytosol.

Arbitrary birefringent metamaterials for holographic optics at λ = 1.55 µm.

This paper presents an optical element capable of multiplexing two diffraction patterns for two orthogonal linear polarizations, based on the use of non-resonant metamaterial cross elements. The metamaterial cross elements provide unique building blocks for engineering arbitrary birefringence. As a proof-of-concept demonstration, we present the design and experimental characterization of a polarization multiplexed blazed diffraction grating and a polarization multiplexed computer-generated hologram, for the telecommunication wavelength of λ = 1.55 µm. A quantitative study of the polarization multiplexed grating reveals that this approach yields a very large polarization contrast ratio. The results show that metamaterials can form the basis for a versatile and compact platform useful in the design of multi-functional photonic devices.

Probing dynamically tunable localized surface plasmon resonances of film-coupled nanoparticles by evanescent wave excitation.

The localized surface plasmon resonance (LSPR) spectrum associated with a gold nanoparticle (NP) coupled to a gold film exhibits extreme sensitivity to the nanogap region where the fields are tightly localized. The LSPR of an ensemble of film-coupled NPs can be observed using an illumination scheme similar to that used to excite the surface plasmon resonance (SPR) of a thin metallic film; however, in the present system, the light is used to probe the highly sensitive distance-dependent LSPR of the gaps between NPs and film rather than the delocalized SPR of the film. We show that the SPR and LSPR spectral contributions can be readily distinguished, and we compare the sensitivities of both modes to displacements in the average gap between a collection of NPs and the gold film. The distance by which the NPs are suspended in solution above the gold film is fixed via a thin molecular spacer layer and can be further modulated by subjecting the NPs to a quasistatic electric field. The observed LSPR spectral shifts triggered by the applied voltage can be correlated with angstrom scale displacements of the NPs, suggesting the potential for chip-scale or flow-cell plasmonic nanoruler devices with extreme sensitivity.

Infrared metamaterial phase holograms.

As a result of advances in nanotechnology and the burgeoning capabilities for fabricating materials with controlled nanoscale geometries, the traditional notion of what constitutes an optical device continues to evolve. The fusion of maturing low-cost lithographic techniques with newer optical design strategies has enabled the introduction of artificially structured metamaterials in place of conventional materials for improving optical components as well as realizing new optical functionality. Here we demonstrate multilayer, lithographically patterned, subwavelength, metal elements, whose distribution forms a computer-generated phase hologram in the infrared region (10.6 µm). Metal inclusions exhibit extremely large scattering and can be implemented in metamaterials that exhibit a wide range of effective medium response, including anomalously large or negative refractive index; optical magnetism; and controlled anisotropy. This large palette of metamaterial responses can be leveraged to achieve greater control over the propagation of light, leading to more compact, efficient and versatile optical components.

Planar, flattened Luneburg lens at infrared wavelengths.

Employing artificially structured metamaterials provides a means of circumventing the limits of conventional optical materials. Here, we use transformation optics (TO) combined with nanolithography to produce a planar Luneburg lens with a flat focal surface that operates at telecommunication wavelengths. Whereas previous infrared TO devices have been transformations of free-space, here we implement a transformation of an existing optical element to create a new device with the same optical characteristics but a user-defined geometry.

Design and fabrication of a metamaterial gradient index diffraction grating at infrared wavelengths.

We demonstrate the design, fabrication and characterization of an artificially structured, gradient index metamaterial with a linear index variation of Δn ~ 3.0. The linear gradient profile is repeated periodically to form the equivalent of a blazed grating, with the gradient occurring across a spatial distance of 61 µm. The grating, which operates at a wavelength of 10.6 µm, is composed of non-resonant, progressively modified "I-beam" metamaterial elements and approximates a linear phase shift gradient using 61 distinguishable phase levels. The grating structure consists of four layers of lithographically patterned metallic I-beam elements separated by dielectric layers of SiO(2). The index gradient is confirmed by comparing the measured magnitudes of the -1, 0 and +1 diffracted orders to those obtained from full wave simulations incorporating all material properties of the metals and dielectrics of the structures. The large index gradient has the potential to enable compact infrared diffractive and gradient index optics, as well as more exotic transformation optical media.

Plasmonic multi-mode interference couplers.

Plasmonic multi-mode interference (MMI) couplers have been investigated both numerically and experimentally at the telecommunication wavelength of 1.55 mum. In this study, the couplers are implemented using thin Au stripes that support long-range surface plasmons. We first detail the operation principle of these devices with numerical simulations and show that useful effects can be obtained despite the high material losses inherent to metallic structures. A series of MMI couplers is subsequently fabricated and experimentally characterized, showing a quantitative agreement with our numerical predictions. We conclude by discussing some of the possible applications for these structures.