ATM phosphorylates PP2A subunit A resulting in nuclear export and spatiotemporal regulation of the DNA damage response.

Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage response (DDR). One critical ATM target is the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A), known to regulate diverse cellular processes such as mitosis and cell growth as well as dephosphorylating many proteins during the recovery from the DDR. We generated mouse embryonic fibroblasts expressing PR65-WT, -S401A (cannot be phosphorylated), and -S401D (phospho-mimetic) transgenes. Significantly, S401 mutants exhibited extensive chromosomal aberrations, impaired DNA double-strand break (DSB) repair and underwent increased mitotic catastrophe after radiation. Both S401A and the S401D cells showed impaired DSB repair (nonhomologous end joining and homologous recombination repair) and exhibited delayed DNA damage recovery, which was reflected in reduced radiation survival. Furthermore, S401D cells displayed increased ERK and AKT signaling resulting in enhanced growth rate further underscoring the multiple roles ATM-PP2A signaling plays in regulating prosurvival responses. Time-lapse video and cellular localization experiments showed that PR65 was exported to the cytoplasm after radiation by CRM1, a nuclear export protein, in line with the very rapid pleiotropic effects observed. A putative nuclear export sequence (NES) close to S401 was identified and when mutated resulted in aberrant PR65 shuttling. Our study demonstrates that the phosphorylation of a single, critical PR65 amino acid (S401) by ATM fundamentally controls the DDR, and balances DSB repair quality, cell survival and growth by spatiotemporal PR65 nuclear-cytoplasmic shuttling mediated by the nuclear export receptor CRM1.

Optomechanical Enhancement of Doubly Resonant 2D Optical Nonlinearity.

Emerging two-dimensional semiconductor materials possess a giant second order nonlinear response due to excitonic effects while the monolayer thickness of such active materials limits their use in practical nonlinear devices. Here, we report 3300 times optomechanical enhancement of second harmonic generation from a MoS2 monolayer in a doubly resonant on-chip optical cavity. We achieve this by engineering the nonlinear light-matter interaction in a microelectro-mechanical system enabled optical frequency doubling device based on an electrostatically tunable Fabry-Perot microresonator. Our versatile optomechanical approach will pave the way for next generation efficient on-chip tunable light sources, sensors, and systems based on molecularly thin materials.

Wavelength tunable microdisk cavity light source with a chemically enhanced MoS2 emitter.

In this work, we report an integrated narrowband light source based on thin MoS2 emissive material coupled to the high quality factor whispering gallery modes of a microdisk cavity with a spatial notch that enables easy out-coupling of emission while it yields high spatial coherence and a Gaussian intensity distribution. The active light emitting material consists of chemically enhanced bilayer MoS2 flakes with a thin atomic layer deposited SiO2 protective coating that yields 20-times brighter chemically enhanced photoluminescence compared to as-exfoliated monolayers on the microdisk. Quality factors ≈ 1000 are observed as well as a high degree of spatial coherence. We also experimentally achieve effective index tuning of cavity coupled emission over a full free spectral range. The thermal response of this system is also studied. This work provides new insights for nanophotonic light sources with atomically thin active media.

Optoelectromechanical multimodal biosensor with graphene active region.

A general, overarching theme in nanotechnology is the integration of multiple disparate fields to realize novel or expanded functionalities. Here, we present a graphene enabled, integrated optoelectromechanical device and demonstrate its utility for biomolecular sensing. We experimentally achieve an ultrawide linear dynamic sensing range of 5 orders of magnitude of protein concentration, an improvement over state-of-the-art single mode nanosensors by approximately 2-3 orders of magnitude, while retaining a subpicomolar lowest detection limit. Moreover, the ability to monitor and characterize adsorption events in the full optoelectromechanical space allows for the extraction of key intrinsic parameters of adsorbates and has the potential to extend the capabilities of nanosensors beyond the traditional binary-valued test for a single type of molecule. This could have significant implications for molecular detection applications at variable concentrations, such as early disease detection in biomedical diagnostics.

Plasmonically enhanced thermomechanical detection of infrared radiation.

Nanoplasmonics has been an attractive area of research due to its ability to localize and manipulate freely propagating radiation on the nanometer scale for strong light-matter interactions. Meanwhile, nanomechanics has set records in the sensing of mass, force, and displacement. In this work, we report efficient coupling between infrared radiation and nanomechanical resonators through nanoantenna enhanced thermoplasmonic effects. Using efficient conversion of electromagnetic energy to mechanical energy in this plasmo-thermomechanical platform with a nanoslot plasmonic absorber integrated directly on a nanobeam mechanical resonator, we demonstrate room-temperature detection of nanowatt level power fluctuations in infrared radiation. We expect our approach, which combines nanoplasmonics with nanomechanical resonators, to lead to optically controlled nanomechanical systems enabling unprecedented functionality in biomolecular and toxic gas sensing and on-chip mass spectroscopy.

Graphene-enabled silver nanoantenna sensors.

Silver is the ideal material for plasmonics because of its low loss at optical frequencies but is often replaced by a more lossy metal, gold. This is because of silver's tendency to tarnish and roughen, forming Ag(2)S on its surface, dramatically diminishing optical properties and rendering it unreliable for applications. By passivating the surface of silver nanostructures with monolayer graphene, atmospheric sulfur containing compounds are unable to penetrate the graphene to degrade the surface of the silver. Preventing this sulfidation eliminates the increased material damping and scattering losses originating from the unintentional Ag(2)S layer. Because it is atomically thin, graphene does not interfere with the ability of localized surface plasmons to interact with the environment in sensing applications. Furthermore, after 30 days graphene-passivated silver (Ag-Gr) nanoantennas exhibit a 2600% higher sensitivity over that of bare Ag nanoantennas and 2 orders of magnitude improvement in peak width endurance. By employing graphene in this manner, the excellent optical properties and large spectral range of silver can be functionally utilized in a variety of nanoscale plasmonic devices and applications.

Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging.

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, because of the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits. Here, we report a transparent, flexible neural electrode technology based on graphene, which enables simultaneous optical imaging and electrophysiological recording. We demonstrate that hippocampal slices can be imaged through transparent graphene electrodes by both confocal and two-photon microscopy without causing any light-induced artefacts in the electrical recordings. Graphene electrodes record high-frequency bursting activity and slow synaptic potentials that are hard to resolve by multicellular calcium imaging. This transparent electrode technology may pave the way for high spatio-temporal resolution electro-optic mapping of the dynamic neuronal activity.

Creating a library of complex metallic nanostructures via harnessing pattern transformation of a single PDMS membrane.

By harnessing the elastic instability in a single PDMS membrane consisting of a square lattice array of circular pores, we fabricated a library of complex nanostructures in Au with variable feature size, connectivity, and geometry, including arrays of diamond-plate patterns (or elliptic herringbones), compound structures of circular dots and elliptical lines, heartbeat waves, aligned ovals, and a rhombus lattice of holes and lines. This was achieved first by swelling the PDMS membrane, followed by convective assembly of nanoparticles on the membrane. By taking advantage of the unique 3-D topography of the nanoparticle film and its photoresist replica, we could gradually etch the photoresist film to vary the feature size and connectivity of the underlying Au patterns. Further, through a combination of mechanical stretching (at different strain levels and stretching angles) and solvent swelling of the same PDMS membrane, we created a richer library of complex patterns in Au without application of new masters.

Electrogenerated chemiluminescence from PbS quantum dots.

We report the first observation of electrogenerated chemiluminescence (ECL) from PbS quantum dots (QDs). Different ECL intensities are observed for different ligands used to passivate the QDs, which indicates that ECL is sensitive to surface chemistry, with the potential to serve as a powerful probe of surface states and charge transfer dynamics in QDs. In particular, passivation of the QD surfaces with trioctylphosphine (TOP) increases ECL intensity by 3 orders of magnitude when compared to passivation with oleic acid alone. The observed overlap of the ECL and photoluminescence spectra suggests a significant reduction of deep surface trap states from the QDs passivated with TOP.