Thermoplasmonic Effect of Surface-Enhanced Infrared Absorption in Vertical Nanoantenna Arrays

Thermoplasmonics is a method for increasing temperature remotely using focused visible or infrared laser beams interacting with plasmonic nanopartides. Here, local heating induced by mid-infrared quantum cascade laser illumination of vertical gold-coated nanoanterma arrays embedded into polymer layers is investigated by infrared nanospectroscopy and electromagnetic/thermal simulations. Nanoscale thermal hotspot images are obtained by a phototherrnal scanning probe microscopy technique with laser illumination wavelength tuned at the different plasmonic resonances of the arrays. Spectral analysis indicates that both Joule heating by the metal antennas and surface-enhanced-infrared absorption (SEIRA) by the polymer molecules located in the apical hotspots of the antennas are responsible for thermoplasmonic resonances, that is, for strong local temperature increase. At odds with more conventional planar nanoantennas, the vertical antenna structure enables thermal decoupling of the hotspot at the antenna apex from the heat sink constituted by the solid substrate. The temperature increase was evaluated by quantitative comparision of data obtained with the photothermal expansion technique to the results of electromagnetic/thermal simulations. In the case of strong SEIRA by the C=O bond of poly-methylmethacrylate at 1730 cm(-1), for focused mid-infrared laser power of about 20 mW, the evaluated order of magnitude of the nanoscale temperature increase is of 10 K. This result indicates that temperature increases of order of hundreds of K may he attainable with full mid-infrared laser power tuned at specific molecule vibrational fingerprints

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies

An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. It contains tumour and matching normal kidney organoids from over 50 children with different subtypes of kidney cancer, including Wilms tumours, malignant rhabdoid tumours, renal cell carcinomas, and congenital mesoblastic nephromas. Paediatric kidney tumour organoids retain key properties of native tumours, useful for revealing patient-specific drug sensitivities. Using single cell RNA-sequencing and high resolution 3D imaging, we further demonstrate that organoid cultures derived from Wilms tumours consist of multiple different cell types, including epithelial, stromal and blastemal-like cells. Our organoid biobank captures the heterogeneity of paediatric kidney tumours, providing a representative collection of well-characterised models for basic cancer research, drug-screening and personalised medicine

Effects of isopropanol on collagen fibrils in new parchment

Background: Isopropanol is widely used by conservators to relax the creases and folds of parchment artefacts. At present, little is known of the possible side effects of the chemical on parchments main structural component- collagen. This study uses X-ray Diffraction to investigate the effects of a range of isopropanol concentrations on the dimensions of the nanostructure of the collagen component of new parchment. Results: It is found in this study that the packing features of the collagen molecules within the collagen fibril are altered by exposure to isopropanol. The results suggest that this chemical treatment can induce a loss of structural water from the collagen within parchment and thus a rearrangement of intermolecular bonding. This study also finds that the effects of isopropanol treatment are permanent to parchment artefacts and cannot be reversed with rehydration using deionised water. Conclusions: This study has shown that isopropanol induces permanent changes to the packing features of collagen within parchment artefacts and has provided scientific evidence that its use to remove creases and folds on parchment artefacts will cause structural change that may contribute to long-term deterioration of parchment artefacts. This work provides valuable information that informs conservation practitioners regarding the use of isopropanol on parchment artefacts

3D nanoporous antennas as a platform for high sensitivity IR plasmonic sensing

Nanoporous gold can be exploited as plasmonic material for enhanced spectroscopy both in the visible and in the near-infrared spectral regions. In particular, the peculiar morphology of such a substrate leads to a higher field confinement with respect to conventional plasmonic materials. This property can be exploited to achieve extremely high sensitivity to the changes in environmental conditions, making it an interesting tool for the development of sensors and biosensors. Here, we compared the sensitivity of a plasmonic resonator made of nanoporous gold with a similar structure made of homogeneous gold. To assess the enhanced sensitivity the same stoichiometric quantity of dielectric material was deposited via Atomic Layer Deposition onto the two considered structures. Experimental results proved the higher sensitivity was achievable using nanoporous gold. In particular. such 3D nanoporous structures can be proposed as a promising sensing platform in the near-infrared with a sensitivity over 4.000 nm/RIU. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Hydration of chloride anions in the NanC Porin from Escherichia coli: A comparative study by QM/MM and MD simulations

Chloride anions permeate the bacterial NanC porin in physiological processes. Here we present a DFT-based QM/MM study of this porin in the presence of these anions. Comparison is made with classical MD simulations on the same system. In both QM/MM and classical approaches, the anions are almost entirely solvated by water molecules. However, the average water–Cl− distance is significantly larger in the first approach. Polarization effects of protein groups close to Cl− anion are sizeable. These effects might modulate the anion-protein electrostatic interactions, which in turn play a central role for selectivity mechanisms of the channel

nMoldyn - Interfacing spectroscopic experiments, molecular dynamics simulations and models for time correlation functions

This article gives an introduction into the program nMoldyn, which has been originally conceived to support the interpretation of neutron scattering experiments on complex molecular systems by the calculation of appropriate time correlation functions from classical and quantum molecular dynamics simulations of corresponding model systems. Later the functionality has been extended to include more advanced time series analyses of molecular dynamics trajectories, in particular the calculation of memory functions, which play an essential role in the theory of time correlation functions. Here we present a synoptic view of the range of applications of the latest version of nMoldyn, which includes new modules for a simulation-based interpretation of data from nuclear magnetic resonance spectroscopy, far infrared spectroscopy and for protein secondary structure analysis

Nanoporous gold metamaterials for high sensitivity plasmonic sensing

Surface plasmon resonance sensors are a well-established class of sensors that includes a very large variety of materials and detection schemes. However, the development of portable devices is still challenging due to the intrinsic complexity of the optical excitation/detection schemes. This work shows that nanoporous gold (NPG) films can overcome the said limitations by providing an excellent sensitivity without the need for sophisticated fabrication approaches and/or optical setups. The sensing mechanism is related to the co-localization of optical energy and analytes in the pores fostering an enhanced light-matter coupling. As a result, when molecules are adsorbed in the pores, the NPG film shows a significant spectral shift of the effective plasma frequency and an abrupt change of the reflectivity. By monitoring the reflectivity in the spectral region close to the plasma frequency (namely the plasma edge), it is possible to detect the analyte. Through a series of experiments, the authors demonstrated a sensitivity exceeding 15 000 nm per RIU in the near infrared range comparable with the state of the art of plasmonic metamaterials

Platination of the copper transporter ATP7A involved in anticancer drug resistance

The clinical efficacy of the widely used anticancer drug cisplatin is severely limited by the emergence of resistance. This is related to the drug binding to proteins such as the copper influx transporter Ctr1, the copper chaperone Atox1, and the copper pumps ATP7A and ATP7B. While the binding modes of cisplatin to the first two proteins are known, the structural determinants of platinated ATP7A/ATP7B are lacking. Here we investigate the interaction of cisplatin with the first soluble domain of ATP7A. First, we establish by ESI-MS and (1)H, (13)C, and (15)N NMR that, in solution, the adduct is a monomer in which the sulfur atoms of residues Cys19 and Cys22 are cis-coordinated to the [Pt(NH3)2](2+) moiety. Then, we carry out hybrid Car-Parrinello QM/MM simulations and computational spectroscopy calculations on a model adduct based on the NMR structure of the apo protein and featuring the experimentally determined binding mode of the metal ion. These calculations show quantitative agreement with CD spectra and (1)H, (13)C, and (15)N NMR chemical shifts, thus providing a quantitative molecular view of the 3D binding mode of cisplatin to ATP7A. Importantly, the same comparison rules out a variety of alternative models with different coordination modes, that we explored to test the robustness of the computational approach. Using this combined in silico-in vitro approach we provide here for the first time a quantitative 3D atomic view of the platinum binding to the first soluble domain of ATP7A