Tuning dipolar and multipolar resonances of chiral silicon nanostructures for control of near field superchirality

Chiral materials display a property called optical activity, which is the capability to interact differentially with left and right circularly polarised light. This leads to the ability to manipulate the polarisation state of light, which has a broad range of applications spanning from energy efficient displays to quantum technologies. Both synthesised and engineered chiral nanomaterials are exploited in such devices. The design strategy for optimising the optical activity of a chiral material is typically based on maximising a single parameter, the electric dipole–magnetic dipole response. Here we demonstrate an alternative approach of controlling optical activity by manipulating both the dipole and multipolar response of a nanomaterial. This provides an additional parameter for material design, affording greater flexibility. The exemplar systems used to illustrate the strategy are nanofabricated chiral silicon structures. The multipolar response of the structures, and hence their optical activity, can be controlled simply by varying their height. This phenomenon allows optical activity and the creation of so called superchiral fields, with enhanced asymmetries, to be controlled over a broader wavelength range, than is achievable with just the electric dipole–magnetic dipole response. This work adds to the material design toolbox providing a route to novel nanomaterials for optoelectronics and sensing applications

Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity

The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease

Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanRASA two-component system, comprising the histidine sensor kinase VanSA and the partner response regulator VanRA. The nature of the activating ligand for VanSA has not been identified, therefore this work sought to identify and characterise ligand(s) for VanSA. In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanSA protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanSA with different affinities (vancomycin 70 μM; teicoplanin 30 and 170 μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanSA, proposing them as activators of type A vancomycin resistance in the enterococci. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.

Selective complexation of divalent cations by a cyclic α,β-peptoid hexamer: a spectroscopic and computational study

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and β-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+)

Membrane remodeling by the M2 amphipathic helix drives influenza virus membrane scission

Membrane scission is a crucial step in all budding processes, from endocytosis to viral budding. Many proteins have been associated with scission, though the underlying molecular details of how scission is accomplished often remain unknown. Here, we investigate the process of M2-mediated membrane scission during the budding of influenza viruses. Residues 50–61 of the viral M2 protein bind membrane and form an amphipathic α-helix (AH). Membrane binding requires hydrophobic interactions with the lipid tails but not charged interactions with the lipid headgroups. Upon binding, the M2AH induces membrane curvature and lipid ordering, constricting and destabilizing the membrane neck, causing scission. We further show that AHs in the cellular proteins Arf1 and Epsin1 behave in a similar manner. Together, they represent a class of membrane-induced AH domains that alter membrane curvature and fluidity, mediating the scission of constricted membrane necks in multiple biological pathways

High-throughput SRCD using multi-well plates and its applications

The sample compartment for high-throughput synchrotron radiation circular dichroism (HT-SRCD) has been developed to satisfy an increased demand of protein characterisation in terms of folding and binding interaction properties not only in the traditional field of structural biology but also in the growing research area of material science with the potential to save time by 80%. As the understanding of protein behaviour in different solvent environments has increased dramatically the development of novel functions such as recombinant proteins modified to have different functions from harvesting solar energy to metabolonics for cleaning heavy and metal and organic molecule pollutions, there is a need to characterise speedily these system

Electronic circular dichroism imaging (CDi) maps local aggregation modes in thin films of chiral oligothiophenes

We highlight the power of electronic circular dichroism imaging (CDi), a technique developed at Diamond Light Source B23 beamline for synchrotron radiation circular dichroism (SRCD) to detect local domains endowed with a chiral supramolecular order in thin films of chiral oligomers and polymers. The highly brilliant and collimated beam light of B23 enabled CDi at a spatial resolution of 0.1 mm, unattainable with benchtop electronic circular dichroism (ECD) spectropolarimeters. CDi is bridging the gap between standard ECD spectroscopy and conventional microscopy. Presently, we apply CDi to reveal the local polymorphism of chiral oligothiophene-based molecules. By extensive use of a post-acquisition data-analysis tool called similarity factor, we quantified the polymorphs revealing a manifold of aggregation pathways whose relative weight was a function of the sample preparation protocol. This work uncovers the parameters that need to be optimised in order to obtain reproducible and controllable supramolecular structures in thin films, which is of paramount importance for materials with optoelectronic properties. It is noteworthy that this analysis is based on CDi measurements at high spatial resolutions of thin films of organic chiral semiconductors at the ultimate stage of preparation as the active layer of an optoelectronic device

Electronic Circular Dichroism Imaging (ECDi) Casts a New Light on the Origin of Solid-State Chiroptical Properties

Solid-state ECD (ss-ECD) spectra of a model microcrystalline solid, finasteride, dispersed into a KCl pellet were recorded by using the synchrotron radiation source at the Diamond B23 beamline. Scanning a surface of 36 mm2 with a step of 0.5 mm, we measured a set of ECD imaging (ECDi) spectra very different from each other and from the ss-ECD recorded with a bench-top instrument (1 cm2 area). This is due to the anisotropic part of the ECD (ACD), which averages to zero in solution or on a large number of randomly oriented crystallites, but can otherwise be extremely large. Two-way singular value decomposition (SVD) analysis, through experimental and simulated TDDFT spectra, disclosed that the measured and theoretical principal components are in line with each other. This finding demonstrates that the observed isotropic ss-ECD spectrum is governed by the anisotropy of locally oriented crystals. It also introduces a new quality for ss-ECD measurements and opens a new future for probing and mapping chiral materials in the solid state such as active pharmaceutical ingredients (APIs)

Optical activity in Ge₂Sb₂Te₅ (GST)

Ge2Sb2Te5 (GST) is an established phase-change material that undergoes fast reversible transitions between amorphous and crystalline states with a high electro-optical contrast, enabling applications in non-volatile optical and electronic memories and optically-switchable structured metamaterials. We have recently demonstrated that optical activity can be induced in pure and doped GST thin films using polarised light, opening up the possibility of controlled induction of anisotropic phase transition in these and related materials for optoelectronic and photonic applications. While the phase transition has generally been understood to proceed via a thermal mechanism, our work strongly suggests that there is an electronic component of crystallization induced by the handedness of circularly polarised nanosecond laser pulses. Significant optical activity in the inorganic thin films, measured by circular dichroism spectroscopy at a synchrotron beamline, implies the existence of chiral structures or motifs. Optically active and inactive regions in the film have been studied using electron diffraction and spectroscopic techniques in order to obtain a structural picture that can be correlated to the optical changes observed. We also propose several mechanisms for the observed effects, which may be extended to other material systems and harnessed in photonic or chiroptical applications