Lasing Emission from Soft Photonic Crystals for Pressure and Position Sensing.

In this report, we introduce a 1D photonic crystal (PhC) nanocavity with waveguide-like strain amplifiers within a soft polydimethylsiloxane substrate, presenting it as a potential candidate for highly sensitive pressure and position optical sensors. Due to its substantial optical wavelength response to uniform pressure, laser emission from this nanocavity enables the detection of a minimum applied uniform pressure of 1.6‱ in experiments. Based on this feature, we further studied and elucidated the distinct behaviors in wavelength shifts when applying localized pressure at various positions relative to the PhC nanocavity. In experiments, by mapping wavelength shifts of the PhC nanolaser under localized pressure applied using a micro-tip at different positions, we demonstrate the nanocavity's capability to detect minute position differences, with position-dependent minimum resolutions ranging from tens to hundreds of micrometers. Furthermore, we also propose and validate the feasibility of employing the strain amplifier as an effective waveguide for extracting the sensing signal from the nanocavity. This approach achieves a 64% unidirectional coupling efficiency for leading out the sensing signal to a specific strain amplifier. We believe these findings pave the way for creating a highly sensitive position-sensing module that can accurately identify localized pressure in a planar space.

Photonic Crystal Polymeric Thin-Film Dye-Lasers for Attachable Strain Sensors.

In this report, using two-dimensional photonic crystals (PhC) and a one-dimensional PhC nano-beam cavity, we realized the development of all-polymeric dye-lasers on a dye-doped, suspended poly-methylmethacrylate film with a wavelength-scale thickness. In addition to the characterization of basic lasing properties, we also evaluated its capacity to serve as an attachable strain sensor. Through experimentation, we confirmed the stable lasing performances of the dye-laser attaching on a rough surface. Moreover, we also theoretically studied the wavelength responses of the utilized PhC resonators to stretching strain and further improved them via the concept of strain shaping. The attachability and high strain sensing response of the presented thin film PhC dye-lasers demonstrate their potential as attachable strain sensors.

MoS2 with Stable Photoluminescence Enhancement under Stretching via Plasmonic Surface Lattice Resonance.

In this study, by combining a large-area MoS2 monolayer with silver plasmonic nanostructures in a deformable polydimethylsiloxane substrate, we theoretically and experimentally studied the photoluminescence (PL) enhancement of MoS2 by surface lattice resonance (SLR) modes of different silver plasmonic nanostructures. We also observed the stable PL enhancement of MoS2 by silver nanodisc arrays under differently applied stretching strains, caused by the mechanical holding effect of the MoS2 monolayer. We believe the results presented herein can guarantee the possibility of stably enhancing the light emission of transition metal dichalcogenides using SLR modes in a deformable platform.

From structure to the dynamic regulation of a molecular switch: A journey over 3 decades.

It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype. We summarize what we have learned since the first structure, published in 1991, why our journey is still ongoing, and why it has been essential to share our structural information. For regulation of kinase activity, we focus on the cAMP-binding protein kinase regulatory subunits. By exploring full-length macromolecular complexes, we discovered not only allostery but also an essential motif originally attributed to crystal packing. Massive genomic data on disease mutations allows us to now revisit crystal packing as a treasure chest of possible protein:protein interfaces where the biological significance and disease relevance can be validated. It provides a new window into exploring dynamic intrinsically disordered regions that previously were deleted, ignored, or attributed to crystal packing. Merging of crystallography with cryo-electron microscopy, cryo-electron tomography, NMR, and millisecond molecular dynamics simulations is opening a new world for the signaling community where those structure coordinates, deposited in the Protein Data Bank, are just a starting point!

Structural analyses of the PKA RIIß holoenzyme containing the oncogenic DnaJB1-PKAc fusion protein reveal protomer asymmetry and fusion-induced allosteric perturbations in fibrolamellar hepatocellular carcinoma.

When the J-domain of the heat shock protein DnaJB1 is fused to the catalytic (C) subunit of cAMP-dependent protein kinase (PKA), replacing exon 1, this fusion protein, J-C subunit (J-C), becomes the driver of fibrolamellar hepatocellular carcinoma (FL-HCC). Here, we use cryo-electron microscopy (cryo-EM) to characterize J-C bound to RIIß, the major PKA regulatory (R) subunit in liver, thus reporting the first cryo-EM structure of any PKA holoenzyme. We report several differences in both structure and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Most striking is the asymmetry caused by the absence of the second cyclic nucleotide binding (CNB) domain and the J-domain in one of the RIIß:J-C protomers. Using molecular dynamics (MD) simulations, we discovered that this asymmetry is already present in the wild-type (WT) RIIß2C2 but had been masked in the previous crystal structure. This asymmetry may link to the intrinsic allosteric regulation of all PKA holoenzymes and could also explain why most disease mutations in PKA regulatory subunits are dominant negative. The cryo-EM structure, combined with small-angle X-ray scattering (SAXS), also allowed us to predict the general position of the Dimerization/Docking (D/D) domain, which is essential for localization and interacting with membrane-anchored A-Kinase-Anchoring Proteins (AKAPs). This position provides a multivalent mechanism for interaction of the RIIß holoenzyme with membranes and would be perturbed in the oncogenic fusion protein. The J-domain also alters several biochemical properties of the RIIß holoenzyme: It is easier to activate with cAMP, and the cooperativity is reduced. These results provide new insights into how the finely tuned allosteric PKA signaling network is disrupted by the oncogenic J-C subunit, ultimately leading to the development of FL-HCC.

Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.

The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.

The In Situ Structure of Parkinson's Disease-Linked LRRK2.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of familial Parkinson's disease. LRRK2 is a multi-domain protein containing a kinase and GTPase. Using correlative light and electron microscopy, in situ cryo-electron tomography, and subtomogram analysis, we reveal a 14-Å structure of LRRK2 bearing a pathogenic mutation that oligomerizes as a right-handed double helix around microtubules, which are left-handed. Using integrative modeling, we determine the architecture of LRRK2, showing that the GTPase and kinase are in close proximity, with the GTPase closer to the microtubule surface, whereas the kinase is exposed to the cytoplasm. We identify two oligomerization interfaces mediated by non-catalytic domains. Mutation of one of these abolishes LRRK2 microtubule-association. Our work demonstrates the power of cryo-electron tomography to generate models of previously unsolved structures in their cellular environment.

Two PKA RIα holoenzyme states define ATP as an isoform-specific orthosteric inhibitor that competes with the allosteric activator, cAMP.

Protein kinase A (PKA) holoenzyme, comprised of a cAMP-binding regulatory (R)-subunit dimer and 2 catalytic (C)-subunits, is the master switch for cAMP-mediated signaling. Of the 4 R-subunits (RIα, RIß, RIIα, RIIß), RIα is most essential for regulating PKA activity in cells. Our 2 RIα2C2 holoenzyme states, which show different conformations with and without ATP, reveal how ATP/Mg2+ functions as a negative orthosteric modulator. Biochemical studies demonstrate how the removal of ATP primes the holoenzyme for cAMP-mediated activation. The opposing competition between ATP/cAMP is unique to RIα. In RIIß, ATP serves as a substrate and facilitates cAMP-activation. The isoform-specific RI-holoenzyme dimer interface mediated by N3A-N3A' motifs defines multidomain cross-talk and an allosteric network that creates competing roles for ATP and cAMP. Comparisons to the RIIß holoenzyme demonstrate isoform-specific holoenzyme interfaces and highlights distinct allosteric mechanisms for activation in addition to the structural diversity of the isoforms.

Structures of the PKA RIα Holoenzyme with the FLHCC Driver J-PKAcα or Wild-Type PKAcα.

Fibrolamellar hepatocellular carcinoma (FLHCC) is driven by J-PKAcα, a kinase fusion chimera of the J domain of DnaJB1 with PKAcα, the catalytic subunit of protein kinase A (PKA). Here we report the crystal structures of the chimeric fusion RIα2:J-PKAcα2 holoenzyme formed by J-PKAcα and the PKA regulatory (R) subunit RIα, and the wild-type (WT) RIα2:PKAcα2 holoenzyme. The chimeric and WT RIα holoenzymes have quaternary structures different from the previously solved WT RIß and RIIß holoenzymes. The WT RIα holoenzyme showed the same configuration as the chimeric RIα2:J-PKAcα2 holoenzyme and a distinct second conformation. The J domains are positioned away from the symmetrical interface between the two RIα:J-PKAcα heterodimers in the chimeric fusion holoenzyme and are highly dynamic. The structural and dynamic features of these holoenzymes enhance our understanding of the fusion chimera protein J-PKAcα that drives FLHCC as well as the isoform specificity of PKA.

Engineering surface lattice resonance of elliptical gold nanodisk array for enhanced strain sensing.

We demonstrate an elliptical gold nanodisk array (GNA) for engineering the spectral profile of surface lattice resonance (SLR). The nanodisk's shape has a great impact on SLR. Small linewidth of 20 nm at an aspect ratio of 1.17, as well as large wavelength tuning of 64 nm within 4% strain via different orientations and polarizations, are achieved experimentally. The enhanced wavelength response of 6.93 nm per 1% strain variation for elliptical GNA is 2.4 times better than that for general circular GNA. Furthermore, the strain sensing for elliptical GNA approaches is 5.7 times greater than that for circular GNA.

Compressible 1D photonic crystal nanolasers with wide wavelength tuning.

We propose and demonstrate a tunable photonic crystal nanolaser consisting of 1D periodic nanorods wrapped in deformable polydimethylsiloxane. In addition to low-threshold and long-term lasing stability, the nanolaser also displays reproducible and reliable wavelength tuning with a large tunability of 7.7 nm under 1% compression. By further associating with stretching, a very wide wavelength-tunable range of 155 nm that almost spans the entire S+C+L telecommunication bands is successfully demonstrated with a single nanolaser device.

Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling.

Scaffolding proteins organize the information flow from activated G protein-coupled receptors (GPCRs) to intracellular effector cascades both spatially and temporally. By this means, signaling scaffolds, such as A-kinase anchoring proteins (AKAPs), compartmentalize kinase activity and ensure substrate selectivity. Using a phosphoproteomics approach we identified a physical and functional connection between protein kinase A (PKA) and Gpr161 (an orphan GPCR) signaling. We show that Gpr161 functions as a selective high-affinity AKAP for type I PKA regulatory subunits (RI). Using cell-based reporters to map protein-protein interactions, we discovered that RI binds directly and selectively to a hydrophobic protein-protein interaction interface in the cytoplasmic carboxyl-terminal tail of Gpr161. Furthermore, our data demonstrate that a binary complex between Gpr161 and RI promotes the compartmentalization of Gpr161 to the plasma membrane. Moreover, we show that Gpr161, functioning as an AKAP, recruits PKA RI to primary cilia in zebrafish embryos. We also show that Gpr161 is a target of PKA phosphorylation, and that mutation of the PKA phosphorylation site affects ciliary receptor localization. Thus, we propose that Gpr161 is itself an AKAP and that the cAMP-sensing Gpr161:PKA complex acts as cilium-compartmentalized signalosome, a concept that now needs to be considered in the analyzing, interpreting, and pharmaceutical targeting of PKA-associated functions.

Trapping particles using waveguide-coupled gold bowtie plasmonic tweezers.

We propose and demonstrate a trapping configuration integrating coupled waveguides and gold bowtie structures to form near-field plasmonic tweezers. Compared with excitation from the top, waves coupled through the waveguide can excite specific bowties on the waveguide and trap particles precisely. Thus this scheme is more efficient and compact, and will assist the circuit design on a chip. With lightning rod and gap effects, the gold bowtie structures can generate highly concentrated resonant fields and induce trapping forces as strong as 652 pN W(-1) on particles with diameters as small as 20 nm. This trapping capability is investigated numerically and verified experimentally with observations of the transport, trapping, and release of particles in the system.

Photonic crystal waveguide cavity with waist design for efficient trapping and detection of nanoparticles.

For manipulating nanometric particles, we propose a photonic crystal waveguide cavity design with a waist structure to enhance resonance characteristic of the cavity. For trapping a polystyrene particle of 50 nm radius on the lateral side of the waist, the optical force can reach 2308 pN/W with 24.7% signal transmission. Threshold power of only 0.32 mW is required for stable trapping. The total length of the device is relatively short with only ten photonic crystal periods, and the trapping can occur precisely and only at the waist. The designed cavity can also provide particle detection and surrounding medium sensing using the transmission spectrum with narrow linewidth. The simulated figure of merit of 110.6 is relatively high compared with those obtained from most plasmonic structures for sensing application. We anticipate this design with features of compact, efficient, and versatile in functionality will be beneficial for developing lab-on-chip in the future.

Molecular switch based on very weak association between BPX26C6 and two recognition units.

A [2]rotaxane has been constructed through metal ion-templated pseudorotaxane formation from a weakly interacting host (bis-p-xylyl[26]crown-6)/guest (diphenylurea derivative) complex and post-assembly modification to form another weakly interacting tertiary ammonium ion recognition site for the host. The combination of this pair of weakly interacting components allowed bifunctional (pH, Na(+) ions) switching of the crown ether unit, highlighting the potential applicability of weakly associated components within molecular switches.

Photonic crystal nanofishbone nanocavity.

We propose a photonic crystal (PhC) nanofishbone (NFB) nanocavity, which confines an ultrahigh Q (~1.8 × 10(7)) transverse-magnetic (TM) mode. With thin slab thickness and only few PhC periods, the TM mode in NFB nanocavity shows higher Q, larger confinement factor and smaller mode volume than that in PhC nanobeam nanocavity, while the total etched-surface area is also significantly reduced. This PhC NFB nanocavity with very compact device size will be very beneficial for quantum cascade lasers, plasmonic nanolasers, and other applications needing high Q TM modes.

Photonic crystal horizontally slotted nanobeam cavity for silicon-based nanolasers.

We theoretically propose and investigate a TM-polarized one-dimensional photonic crystal nanocavity with a horizontal SiO2 slot on a suspended silicon nanobeam via the three-dimensional finite-element method. The ultrahigh quality factor and ultrasmall effective mode volume of 1.5×10(7) and 0.176 half-wavelength cubic of the horizontally SiO2-slotted nanocavity show strong possibilities for realizing an erbium-doped SiO2 nanolaser. This horizontal SiO2 slot structure can be precisely formed via the sputtering process and further transformed into an air slot via selective wet etching for optical index and biomolecule sensing.

Plasmonic coupling in gold nanoring dimers: observation of coupled bonding mode.

We investigate the optical properties of gold nanoring (NR) dimers in both simulation and experiment. The resonance peak wavelength of gold NR dimers is strongly dependent on the polarization direction and gap distance. As the gold NR particles approach each other, exponential red shift and slight blue shift of coupled bonding (CB) mode in gold NR dimers for longitudinal and transverse polarizations are obtained. In finite element method analysis, a very strong surface plasmon coupling in the gap region of gold NR dimers is observed, whose field intensity at the gap distance of 10 nm is enhanced 23% compared to that for gold nanodisk (ND) dimers with the same diameter. In addition, plasmonic dimer system exhibits a great improvement in the sensing performance. Near-field coupling in gold NR dimers causes exponential increase in sensitivity to refractive index of surrounding medium with decreasing the gap distance. Compared with coupled dipole mode in gold ND dimers, CB mode in gold NR dimers shows higher index sensitivity. This better index sensing performance is resulted form the additional electric field in inside region of NR and the larger field enhancement in the gap region owing to the stronger coupling of collective dipole plasmon resonances for CB mode. These results pave the way to design plasmonic nanostructures for practical applications that require coupled metallic nanoparticles with enhanced electric fields.

Square lattice photonic crystal surface mode lasers.

In this report, we propose a square lattice photonic crystal hetero-slab-edge microcavity design. In numerical simulations, three surface modes in this microcavity are investigated and optimized by tuning the slab-edge termination τ and gradual mirror layer. High simulated quality (Q) factor of 2.3 × 10(5) and small mode volume of 0.105 µm(3) are obtained from microcavity with τ = 0.80. In experiments, we obtain and identify different surface modes lasing. The surface mode in the second photonic band gap shows a very-low threshold of 140 µW and high Q factor of 5,500, which could be an avenue to low-threshold optical lasers and highly sensitive sensor applications with efficient light-matter interactions.