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In a recent study, spectroscopic observations of modified cholesterol in both lipid-coated nanoparticles and liposomes provided evidence for a disorder-to-order orientational transition with increasing temperature. Below a critical temperature, in a membrane composed of modified cholesterol, saturated (DPPC) lipid, and anionic (DOPS) lipid, a roughly equal population of head-out and head-in conformations was observed. Surprisingly, as temperature was increased the modified cholesterol presented an abrupt transition to a population of all head-in orientations. Additionally, when saturated DPPC lipids were replaced by unsaturated DOPC the disorder-to-order transition was eliminated. To gain insight into this curious transition, we use all-atom molecular dynamics simulations to characterize the structure and fluctuations of lipid bilayers composed of saturated and unsaturated lipids, in the presence of normal and modified cholesterol. Free energy differences between head-out and head-in conformations are computed as a function of varying lipid membrane composition for normal and modified cholesterol. In bilayers primarily composed of DPPC, the orientation of modified cholesterol is observed to depend sensitively on the orientation of the surrounding normal or modified cholesterol molecules, suggesting cooperative Ising-like interactions favoring an ordered state. In bilayers primarily composed of DOPC, spontaneous flip-flop of modified cholesterol is observed, consistent with the measured small free energy barrier separating the head-in and head-out orientations. This combined experimental and computational study effectively characterizes the orientational dimorphism and provides novel insight into the fundamental nature of cholesterol interactions in membrane.

Hybrid nanomaterials containing both noble metal and semiconductor building blocks provide an engineerable platform for realizing direct or indirect charge and energy transfer for enhanced plasmonic photoconversion and photocatalysis. In this work, silver nanoparticles (AgNPs) and chalcopyrite (CuFeS 2 ) nanocrystals (NCs) are combined into a AgNP@CuFeS 2 hybrid structure comprising NCs embedded in a self-assembled lipid coating around the AgNP core. In AgNP@CuFeS 2 hybrid structures, both metallic and semiconductor NCs support quasistatic resonances. To characterize the interactions between these resonances and their effect on potential charge and energy transfer, direct interfacial excitation transfer between the AgNP core and surrounding CuFeS 2 NCs is probed through single particle line shape analysis and supporting electromagnetic simulations. These studies reveal that CuFeS 2 NCs localized in the evanescent field of the central AgNP induce a broadening of the metal NP line shape that peaks when an energetic match between the AgNP and CuFeS 2 NC resonances maximizes direct energy transfer. Dimers of AgNPs whose resonances exhibit poor energetic overlap with the CuFeS 2 NC quasistatic resonance yield much weaker line shape broadening in a control experiment, corroborating the existence of resonant energy transfer in the AgNP@CuFeS 2 hybrid. Resonant coupling between the metallic and semiconductor building blocks in the investigated hybrid architecture provides a mechanism for utilizing the large optical cross-section of the central AgNP to enhance the generation of reactive charge carriers in the surrounding semiconductor NCs for potential applications in photocatalysis.

Plasmonic molecules are discrete assemblies of noble metal nanoparticles (NPs) that are of interest as transducers in optical nanosensors. So far, NPs with diameters of ∼40 nm have been the preferred building blocks for plasmonic molecules intended as optical single molecule sensors due to difficulties associated with detecting smaller NPs through elastic scattering in conventional darkfield microscopy. Here, we apply 405 nm, 445 nm two-color interferometric scattering (iSCAT) microscopy to characterize polyethylene glycol (PEG) tethered dimers of 10 nm and 20 nm Ag NPs and their monomers. Dimers of both NP sizes can be discerned from their respective monomers through changes in the average iSCAT contrast. In the case of 20 nm Ag NPs, dimer formation induces a change in the sign of the iSCAT contrast, providing a characteristic signal for detecting binding events. 20 nm Ag NP dimers with 0.4 kDa and 3.4 kDa polyethylene glycol (PEG) spacers show iSCAT contrast distributions with significantly different averages on both wavelength channels. The iSCAT contrast measured for individual PEG-tethered 10 nm or 20 nm NP dimers as a function of time shows contrast fluctuations indicative of a rich structural dynamics in the assembled plasmonic molecules, which provides an additional metric to discern dimers from monomers and paves the path to a new class of interferometric plasmon rulers.

Lipid coating is considered a versatile strategy to equip nanoparticles (NPs) with a biomimetic surface coating, but the membrane properties of these nanoassemblies remain in many cases insufficiently understood. In this work, we apply C-Laurdan generalized polarization (GP) measurements to probe the temperature-dependent polarity of hybrid membranes consisting of a lipid monolayer adsorbed onto a polylactic acid (PLA) polymer core as function of lipid composition and compare the behavior of the lipid coated NPs (LNPs) with that of liposomes assembled from identical lipid mixtures. The LNPs were generated by nanoprecipitation of the polymer in aqueous solutions containing two types of lipid mixtures: (i) cholesterol, dipalmitoylphosphatidylcholine (DPPC), and the ganglioside GM3, as well as (ii) dioleoylphosphatidylcholine (DOPC), DPPC and GM3. LNPs were found to exhibit more distinct and narrower phase transitions than corresponding liposomes and to retain detectable phase transitions even for cholesterol or DOPC concentrations that yielded no detectable transitions in liposomes. These findings together with higher GP values in the case of the LNPs for temperatures above the phase transition temperature indicate a stabilization of the membrane through the polymer core. LNP binding studies to GM3-recognizing cells indicate that differences in the membrane fluidity affect binding avidity in the investigated model system.

Optical sensors and sensing technologies are playing a more and more important role in our modern world. From micro-probes to large devices used in such diverse areas like medical diagnosis, defence, monitoring of industrial and environmental conditions, optics can be used in a variety of ways to achieve compact, low cost, stand-off sensing with extreme sensitivity and selectivity. Actually, the challenges to the design and functioning of an optical sensor for a particular application requires intimate knowledge of the optical, material, and environmental properties that can affect its performance. This roadmap on optical sensors addresses different technologies and application areas. It is constituted by twelve contributions authored by world-leading experts, providing insight into the current state-of-the-art and the challenges their respective fields face. Two articles address the area of optical fibre sensors, encompassing both conventional and specialty optical fibres. Several other articles are dedicated to laser-based sensors, micro- and nano-engineered sensors, whispering-gallery mode and plasmonic sensors. The use of optical sensors in chemical, biological and biomedical areas is discussed in some other papers. Different approaches required to satisfy applications at visible, infrared and THz spectral regions are also discussed., (© 2023 The Author(s). Published by IOP Publishing Ltd.)

The ability to discern noble metal nanoparticles (NPs) with different sizes and in ambient media with different refractive indices has important applications in imaging and sensing. Here a two-color (405 nm, 445 nm) interferometric scattering (iSCAT) detection scheme is applied to characterize the wavelength-dependent iSCAT contrast of Ag NPs with nominal diameters of 10, 20, 40, and 60 nm and to distinguish between NPs of different sizes. The iSCAT contrast also depends on the ambient refractive index and the relative iSCAT contrast on both channels revealed a spectral red-shift for 40 and 60 nm Ag NPs when the ambient refractive index was increased from n = 1.3892 to n = 1.4328. With the selected wavelength channels, the spectral resolution of the two-color imaging strategy was, however, insufficient to resolve spectral shifts induced by refractive index changes for 10 and 20 nm Ag NPs.

Despite increasing efforts to recycle plastic materials, large quantities of plastics waste continue to accumulate in the oceans. Persistent mechanical and photochemical degradation of plastics in the oceans yields micro- and nanoscale plastic particles, which represent potential vectors for mobilizing hydrophobic carcinogens in an aqueous milieu. Yet, the fate and potential threats associated with plastics remain largely unexplored. Herein, we apply an accelerated weathering protocol to consumer plastics to characterize the effect of photochemical weathering on the size, morphology, and chemical composition of nanoplastics under defined conditions and validate that the photochemical degradation is consistent with plastics harvested from the Pacific Ocean. Machine learning algorithms trained with accelerated weathering data successfully classify weathered plastics from nature. We demonstrate that photodegradation of poly(ethylene terephthalate) (PET)-containing plastics produces enough CO 2 to induce a mineralization process that results in the deposition of CaCO 3 on nanoplastics. Finally, we determine that despite UV-radiation induced photochemical degradation and mineral deposition, nanoplastics retain their ability to sorb, mobilize, and increase bioaccessibility of polycyclic aromatic hydrocarbons (PAHs) in water and under simulated physiological gastric and intestinal conditions.

Chimeric Antigen Receptor (CAR) T cell therapy has proven to be an effective strategy against hematological malignancies but persistence and activity against solid tumors must be further improved. One emerging strategy for enhancing efficacy is based on directing CAR T cells to antigen presenting cells (APCs). Activation of CAR T cells at the immunological synapse (IS) formed between APC and T cell is thought to promote strong, persistent antigen-specific T cell-mediated immune responses but requires integration of CAR ligands into the APC/T-cell interface. Here, we demonstrate that CAR ligand functionalized, lipid-coated, biodegradable polymer nanoparticles (NPs) that contain the ganglioside GM3 (GM3-NPs) bind to CD169 (Siglec-1)-expressing APCs and localize to the cell contact site between APCs and CAR T cells upon initiation of cell conjugates. The CD169 + APC/CAR T-cell interface is characterized by a strong optical colocalization of GM3-NPs and CARs, enrichment of F-actin, and recruitment of ZAP-70, indicative of integration of GM3-NPs into a functional IS. Ligands associated with GM3-NPs localized to the APC/T-cell contact site remain accessible to CARs and result in robust T-cell activation. Overall, this work identifies GM3-NPs as a potential antigen delivery platform for active targeting of CD169 expressing APCs and enhancement of CAR T-cell activation at the NP-containing IS.

The epidermal growth factor (EGF) receptor (EGFR) is heterogeneously distributed on the cellular surface and enriched in clusters with diameters of tens of nanometers. Multivalent presentation of EGF ligand on nanoparticles (NPs) provides an approach for controlling and amplifying the local activation of EGFR in these clusters. Reactive oxygen species (ROS) have been indicated to play a role in the regulation of EGFR activation as second messengers, but the effect of nanoconjugation on EGF-mediated ROS formation and ROS-induced EGFR activation is not well established. The goal of this manuscript is to characterize the multivalent enhancement of EGF-induced ROS formation and to test its effect on EGFR phosphorylation in breast cancer cell models using gold (Au) NPs with a diameter of 81 ± 1 nm functionalized with two different EGF ligand densities (12 ± 7 EGF/NP (NP-EGF 12 ) and 87 ± 6 EGF/NP (NP-EGF 87 )). In the EGFR overexpressing cell lines MDA-MB-231 and MDA-MB-468, NP-EGF 87 achieved a measurable multivalent enhancement of ROS that peaked at concentrations c ROS max ≤ 25 pM and that were EGFR and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent. NP-EGF 12 failed to generate comparable ROS levels as NP-EGF 87 in the investigated NP input concentration range (0-100 pM). In cells with nearly identical numbers of bound NP-EGF 87 and NP-EGF 12 , the ROS levels for NP-EGF 87 were systematically higher, indicating that the multivalent enhancement is exclusively related not only to avidity but also to a stronger stimulation per NP. Importantly, the increase in EGF-induced ROS formation associated with EGF nanoconjugation at c ROS max resulted in a measurable gain in EGFR phosphorylation, confirming that ROS generation contributes to the multivalent enhancement of EGFR activation in response to NP-EGF 87 .

Herein, lipid-coated mesoporous silica nanoparticles (LMSN) are investigated as biomimetic delivery vehicle for two antiretroviral compounds (ARVs), rilpivirine (RPV) and cabotegravir (CAB). Monosialodihexosylganglioside (GM3) is incorporated into the membrane to facilitate LMSN binding to CD169 (Siglec-1)-expressing myeloid cells, that are predominantly expressed in secondary lymphoid tissues in vivo . It is demonstrated that in addition to providing CD169-binding functionalities, the lipid membrane around the silica core provides stealth properties that dampen the inflammatory cytokine response to ARVs-loaded LMSN in human monocyte-derived macrophages. Quantification of RPV and CAB releases from nanoparticles, and assessment of antiviral potency to human immunodeficiency virus (HIV-1) infection in vitro reveals that RPV and CAB co-formulated into LMSN retain optimal antiviral potency for 90 days, even upon storage at room temperature, making LMSN an attractive nanoplatform, immune to cold chain requirements. These findings suggest that GM3-LMSN equip the mesoporous silica nanoparticle (MSN) core with lipid-derived properties for surface passivation and lipid-mediated binding that are of high interest for achieving an effective delivery of ARVs to tissue reservoirs of HIV-1 replication., Competing Interests: Conflict of Interest B.M.R. and S.G. hold patents for GM3 functionalized nanoparticles.

Excited, or "hot" charge carrier generation and transfer driven by the decay of localized surface plasmon resonances (LSPRs) are key steps in plasmonic photocatalysis. Hybrid structures that contain both metal and semiconductor building blocks facilitate the extraction of reactive charge carriers and their utilization for photoelectrocatalysis. Additional functionality arises from hybrid structures that combine noble metal nanostructures with semiconductor components, such as chalcopyrite (CuFeS 2 ) nanocrystals (NCs), which by themselves support quasistatic resonances. In this work, we use a hybrid membrane to integrate Au nanorods (NRs) with a longitudinal LSPR at 745 nm and CuFeS 2 NCs with a resonance peak at 490 nm into water-stable nanocomposites for robust and bifunctional photocatalysis of oxygen and hydrogen evolution reactions in a wavelength-dependent manner. Excitation of NRs or NCs in the nanocomposite correlates with increased hydrogen or oxygen evolution, respectively, consistent with a light-driven electron transfer between the metal and semiconductor building blocks, the direction of which depends on the wavelength. The bifunctional photoreactivity of the nanocomposite is enhanced by Cu(I)/Cu(II)-assisted catalysis on the surface of the NCs.

Plastic materials are ubiquitous in medical devices and consumer goods. As bacterial contamination of plastic surfaces can pose significant health risks, there is a need for effective approaches both to inactivate bacteria on plastic surfaces and to prevent colonization of plastic surfaces. In this study, we evaluate a plasmonic photoreactor coating for plastic surfaces that provides both active and passive antimicrobial effects and implement a visible light-driven antibacterial flow sterilizer. We demonstrate that this approach inactivates bacteria in an aqueous suspension passed through a photoreactor-coated polyethylene tubing, achieving log reduction values (LRVs) > 5 for both Gram-positive and -negative bacteria under resonant LED illumination. Importantly, the antimicrobial flow sterilizers do not cause a detectable loss of functionality for monoclonal antibodies that were included in this work as an example of high-value biologics that require sterilization. Under ambient light illumination, the plasmonic photoreactor coating exhibits a significant inhibitory effect on bacterial colonization and biofilm formation. The inhibitory effect was substantially weaker for mammalian cells, indicating some selectivity in the protection provided by the coating.

Light can be an effective antimicrobial. UV-C light, in particular, is now commonly used to sterilize inanimate surfaces, water, and even air. Highly energetic light can, however, also lead to unwanted photodamage and be hazardous. Consequently, conventional light-mediated microbe inactivation is not suitable for all applications. Plasmonic nanostructures can enhance electromagnetic fields in the visible range of the electromagnetic spectrum and show unique light-induced responses that can drive strong antimicrobial effects even for wavelengths that without plasmonic enhancement have little to no antimicrobial impact. Plasmonic nanostructures offer thus a potential strategy to expand the antimicrobial effect of light to wavelength and intensity ranges in which light-associated collateral damages are lower. This Perspective examines selected plasmon-enhanced antimicrobial strategies, elucidates the underlying physico-chemical mechanisms, and discusses applications., Competing Interests: Competing Interests B.M.R has filed a patent for “Photonic Inactivation of Pathogens”.

Monosialodihexosylganglioside (GM3)-presenting lipid-coated polymer nanoparticles (NPs) that recapitulate the sequestration of human immunodeficiency virus-1 (HIV-1) particles in CD169 + virus-containing compartments (VCCs) of macrophages were developed as carriers for delivery and sustained release of a combination of two antiretrovirals (ARVs), rilpivirine (RPV) and cabotegravir (CAB). RPV and CAB were co-loaded into GM3-presenting lipid-coated polylactic acid (PLA) and poly(lactic- co -glycolic acid) (PLGA) NPs without loss in potency of the drugs. GM3-presenting PLA NPs demonstrated the most favorable release properties and achieved inhibition of HIV-1 infection of primary human macrophages for up to 35 days. Intracellular localization of GM3-presenting PLA NPs in VCCs correlated with retention of intracellular ARV concentrations and sustained inhibition of HIV-1 infection. This work elucidates the design criteria of lipid-coated polymer NPs to utilize CD169 + macrophages as cellular drug depots for eradicating the viral reservoir sites or to achieve long-acting prophylaxis against HIV-1 infection.

Lipid-coated noble metal nanoparticles (L-NPs) combine the biomimetic surface properties of a self-assembled lipid membrane with the plasmonic properties of a nanoparticle (NP) core. In this work, we investigate derivatives of cholesterol, which can be found in high concentrations in biological membranes, and other terpenoids, as tunable, synthetic platforms to functionalize L-NPs. Side chains of different length and polarity, with a terminal alkyne group as Raman label, are introduced into cholesterol and betulin frameworks. The synthesized tags are shown to coexist in two conformations in the lipid layer of the L-NPs, identified as "head-out" and "head-in" orientations, whose relative ratio is determined by their interactions with the lipid-water hydrogen-bonding network. The orientational dimorphism of the tags introduces orthogonal functionalities into the NP surface for selective targeting and plasmon-enhanced Raman sensing, which is utilized for the identification and Raman imaging of epidermal growth factor receptor-overexpressing cancer cells., Competing Interests: The authors declare no competing interest.

Bacterial, viral and fungal infections pose serious threats to human health and well-being. The continuous emergence of acute infectious diseases caused by pathogenic microbes and the rapid development of resistances against conventional antimicrobial drugs necessitates the development of new and effective strategies for the safe elimination of microbes in water, food or on surfaces, as well as for the inactivation of pathogenic microbes in human hosts. The need for new antimicrobials has triggered the development of plasmonic nano-antimicrobials that facilitate both light-dependent and -independent microbe inactivation mechanisms. This review introduces the relevant photophysical mechanisms underlying these plasmonic nano-antimicrobials, and provides an overview of how the photoresponses and materials properties of plasmonic nanostructures can be applied in microbial pathogen inactivation and sensing applications. Through a systematic analysis of the inactivation efficacies of different plasmonic nanostructures, this review outlines the current state-of-the-art in plasmonic nano-antimicrobials and defines the application space for different microbial inactivation strategies. The advantageous optical properties of plasmonic nano-antimicrobials also enhance microbial detection and sensing modalities and thus help to avoid exposure to microbial pathogens. Sensitive and fast plasmonic microbial sensing modalities and their theranostic and targeted therapeutic applications are discussed.

Despite the extensive use of biodegradable polyester nanoparticles for drug delivery, and reports of the strong influence of nanoparticle mechanics on nano-bio interactions, there is a lack of systematic studies on the mechanics of these nanoparticles under physiologically relevant conditions. Here, we report indentation experiments on poly(lactic acid) and poly(lactide- co -glycolide) nanoparticles using atomic force microscopy. While dried nanoparticles were found to be rigid at room temperature, their elastic modulus was found to decrease by as much as 30 fold under simulated physiological conditions (i.e., in water at 37 °C). Differential scanning calorimetry confirms that this softening can be attributed to the glass transition of the nanoparticles. Using a combination of mechanical and thermoanalytical characterization, the plasticizing effects of miniaturization, molecular weight, and immersion in water were investigated. Collectively, these experiments provide insight for experimentalists exploring the relationship between polymer nanoparticle mechanics and in vivo behavior.

The monosialodihexosylganglioside, GM3, and its binding to CD169 (Siglec-1) have been indicated as key factors in the glycoprotein-independent sequestration of the human immunodeficiency virus-1 (HIV-1) in virus-containing compartments (VCCs) in myeloid cells. Here, lipid-wrapped polymer nanoparticles (NPs) are applied as a virus-mimicking model to characterize the effect of core stiffness on NP uptake and intracellular fate triggered by GM3-CD169 binding in macrophages. GM3-functionalized lipid-wrapped NPs are assembled with poly(lactic- co -glycolic) acid (PLGA) as well as with low and high molecular weight polylactic acid (PLA lMW and PLA hMW ) cores. The NPs have an average diameter of 146 ± 17 nm and comparable surface properties defined by the self-assembled lipid layer. Due to differences in the glass transition temperature, the Young's modulus ( E ) differs substantially under physiological conditions between PLGA ( E PLGA  = 60 ± 32 MPa), PLA lMW ( E PLA lMW  = 86 ± 25 MPa), and PLA hMW ( E PLA hMW  = 1.41 ± 0.67 GPa) NPs. Only the stiff GM3-presenting PLA hMW NPs but not the softer PLGA or PLA lMW NPs avoid a lysosomal pathway and localize in tetraspanin (CD9)-positive compartments that resemble VCCs. These observations suggest that GM3-CD169-induced sequestration of NPs in nonlysosomal compartments is not entirely determined by ligand-receptor interactions but also depends on core stiffness., Competing Interests: S.G. and B.M.R. hold a patent for GM3‐functionalized nanoparticles., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bimetallic plasmonic nanostructures provide composition and spatial distribution of the individual components in the nanostructure in addition to overall size and morphology as degrees of freedom for tuning near- and far-field optical responses. AgAuAg nanorods (NRs) generated through epitaxial deposition of Ag on the tips of Au bipyramids (BPs) are an important bimetallic model system whose longitudinal dipolar plasmon mode first shows a spectral blue-shift upon initial deposition of Ag on the Au BP tips followed by a red-shift after additional deposition of Ag. Here, we quantify the relative contributions from morphological and compositional effects to the far-field spectral shift of the longitudinal and vertical dipolar plasmon modes during the initial deposition of Ag and compare the near-field in Ag and AgAuAg NRs with lengths between L = 130 nm-280 nm under whitelight illumination through electromagnetic simulations. Subsequently, we experimentally characterize the near-field around AgAuAg NRs with lengths between L = 88.1-749.0 nm at a constant excitation wavelength of 1064 nm on a silicon (Si) support through scattering type near-field scanning microscopy (sNSOM). We detect Fabry-Perot resonance-like higher order multipolar plasmon resonances whose order and near-field pattern depends on the length and composition of the NRs as well as the refractive index of the ambient medium. We find that under oblique illumination higher order multipolar modes with an even symmetry dominate on the high refractive index Si substrate due to strong electromagnetic interactions between the NR and the substrate.

Photocatalytic compounds and complexes, such as tris(bipyridine)ruthenium(II), [Ru(bpy) 3 ] 2+ , have recently attracted attention as light-mediated bactericides that can help to address the need for new antibacterial strategies. We demonstrate in this work that the bactericidal efficacy of [Ru(bpy) 3 ] 2+ and the control of its antibacterial function can be significantly enhanced through combination with a plasmonic nanoantenna. We report strong, visible light-controlled bacterial inactivation with a nanocomposite design that incorporates [Ru(bpy) 3 ] 2+ as a photocatalyst and a Ag nanoparticle (NP) core as a light-concentrating nanoantenna into a plasmonic hybrid photoreactor. The hybrid photoreactor platform is facilitated by a self-assembled lipid membrane that encapsulates the Ag NP and binds the photocatalyst. The lipid membrane renders the nanocomposite biocompatible in the absence of resonant illumination. Upon illumination, the plasmon-enhanced photoexcitation of the metal-to-ligand charge-transfer band of [Ru(bpy) 3 ] 2+ prepares the reactive excited state of the complex that oxidizes the nanocomposite membrane and increases its permeability. The photooxidation induces the release of [Ru(bpy) 3 ] 2+ , Ag + , and peroxidized lipids into the ambient medium, where they interact synergistically to inactivate bacteria. We measured a 7 order of magnitude decrease in Gram-positive Arthrobacter sp. and a 4 order of magnitude decrease in Gram-negative Escherichia coli colony forming units with the photoreactor bactericides after visible light illumination for 1 h. In both cases, the photoreactor exceeds the bactericidal standard of a log reduction value of 3 and surpasses the antibacterial effect of free Ag NPs or [Ru(bpy) 3 ] 2+ by >4 orders of magnitude. We also implement the inactivation of a bacterial thin film in a proof-of-concept study.

Spatial clustering of cell membrane receptors has been indicated to play a regulatory role in signal initiation, and the distribution of receptors on the cell surface may represent a potential biomarker. To realize its potential for diagnostic purposes, scalable assays capable of mapping spatial receptor heterogeneity with high throughput are needed. In this work, we use gold nanoparticle (NP) labels with an average diameter of 72.17 ± 2.16 nm as bright markers for large-scale epidermal growth factor receptor (EGFR) clustering in hyperspectral plasmon coupling microscopy and compare the obtained clustering maps with those obtained through fluorescence superresolution microscopy (direct stochastic optical reconstruction microscopy, dSTORM). Our dSTORM experiments reveal average EGFR cluster sizes of 172 ± 99 and 150 ± 90 nm for MDA-MB-468 and HeLa, respectively. The cluster sizes decrease after EGFR activation. Hyperspectral imaging of the NP labels shows that differences in the EGFR cluster sizes are accompanied by differences in the average separations between electromagnetically coupled NPs. Because of the distance dependence of plasmon coupling, changes in the average interparticle separation result in significant spectral shifts. For the experimental conditions investigated in this work, hyperspectral plasmon coupling microscopy of NP labels identified the same trends in large-scale EGFR clustering as dSTORM, but the NP imaging approach provided the information in a fraction of the time. Both dSTORM and hyperspectral plasmon coupling microscopy confirm the cortical actin network as one structural component that determines the average size of EGFR clusters.

The T cell Ig and mucin domain (TIM) proteins inhibit release of HIV-1 and other enveloped viruses by interacting with cell- and virion-associated phosphatidylserine (PS). Here, we show that the Nef proteins of HIV-1 and other lentiviruses antagonize TIM-mediated restriction. TIM-1 more potently inhibits the release of Nef-deficient relative to Nef-expressing HIV-1, and ectopic expression of Nef relieves restriction. HIV-1 Nef does not down-regulate the overall level of TIM-1 expression, but promotes its internalization from the plasma membrane and sequesters its expression in intracellular compartments. Notably, Nef mutants defective in modulating membrane protein endocytic trafficking are incapable of antagonizing TIM-mediated inhibition of HIV-1 release. Intriguingly, depletion of SERINC3 or SERINC5 proteins in human peripheral blood mononuclear cells (PBMCs) attenuates TIM-1 restriction of HIV-1 release, in particular that of Nef-deficient viruses. In contrast, coexpression of SERINC3 or SERINC5 increases the expression of TIM-1 on the plasma membrane and potentiates TIM-mediated inhibition of HIV-1 production. Pulse-chase metabolic labeling reveals that the half-life of TIM-1 is extended by SERINC5 from <2 to ∼6 hours, suggesting that SERINC5 stabilizes the expression of TIM-1. Consistent with a role for SERINC protein in potentiating TIM-1 restriction, we find that MLV glycoGag and EIAV S2 proteins, which, like Nef, antagonize SERINC-mediated diminishment of HIV-1 infectivity, also effectively counteract TIM-mediated inhibition of HIV-1 release. Collectively, our work reveals a role of Nef in antagonizing TIM-1 and highlights the complex interplay between Nef and HIV-1 restriction by TIMs and SERINCs., Competing Interests: The authors declare no conflict of interest.

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor prognosis due to lack of druggable targets such as hormone and growth factor receptors. Therefore, identification of targetable regulators such as miRNAs could provide new avenues for therapeutic applications. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. MiR-4417 is localized to chromosome 1p36, a region with high frequency of loss of heterozygosity in multiple cancers, and its biogenesis is DICER-dependent. Low expression of miR-4417 is significantly associated with worse prognosis in TNBC patients, while overexpression of miR-4417 is sufficient to inhibit migration and mammosphere formation of TNBC cells in vitro . Overall, our findings suggest miR-4417 exerts a tumor suppressive effect and thereby could serve as a prognostic biomarker and therapeutic tool against TNBC.

Multivalent presentation of ligands on nanoparticles (NPs) is considered a general strategy for enhancing receptor binding and activation through amplification of ligand-receptor interactions within the footprint of the individual NPs. The spatial clustering of ligand-functionalized NPs represents an additional, less well understood mechanism for increasing local ligand-receptor interactions, especially for receptors that form higher-order assemblies, such as the epidermal growth factor (EGF) receptor (EGFR). To shed light on the interplay between ligand density ( i.e., multivalency) and NP clustering in signal amplification, we apply EGF-functionalized 72 ± 1 nm gold nanoparticles (NP-EGF) with known ligand loading (10-200 EGF/NP) as quantifiable and experimentally tractable units of EGFR activation and characterize the NP-mediated amplification of EGFR phosphorylation as a function of both EGF surface density and NP-EGF clustering for two cancer cell lines (HeLa and MDA-MB-468). The measurements confirm a strong multivalent amplification of EGFR phosphorylation through NP-EGF on the cellular level that results in EGF-loading-dependent maximum EGFR phosphorylation levels. A microscopic analysis of NP-EGF-induced EGFR phosphorylation reveals a heterogeneous spatial distribution of EGFR activation across the cell surface. Clustering of multivalent NP-EGF on sub-diffraction-limited length scales is found to result in a local enhancement of EGFR phosphorylation in signaling "hot spots" from where the signal can spread laterally in an EGF-independent fashion. Increasing EGF loadings of the NP enhances NP-EGF clustering and intensifies EGFR phosphorylation. These observations suggest that NP-EGF clustering and the associated local enhancement of ligand-receptor interactions are intrinsic components of the multivalent amplification of phosphorylation for the heterogeneously distributed EGFR through NP-EGF.

Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial virus nanoparticles (AVNs) that combine the large nonblinking or bleaching optical cross-section of the NP core with the biological surface properties and functionalities provided by a self-assembled lipid membrane. We used these hybrid nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)-expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane decreases binding. Molecular dynamics simulations of the AVN membrane and experimental binding studies of CD169 to GM3-presenting AVNs reveal Na + -mediated interactions between GM3 and PS as a potential cause of the antagonistic action on binding by the two negatively charged lipids. GM3-functionalized AVNs with no or low PS content localize to tetherin + , CD9 + VCC in a membrane composition-depending fashion, but increasing amounts of PS in the AVN membrane redirect the NP to lysosomal compartments. Interestingly, this compartmentalization is highly GM3 specific. Even AVNs presenting the related monosialotetrahexosylganglioside (GM1) fail to achieve an accumulation in VCC. AVN localization to VCC was observed for AVN with gold NP core but not for liposomes, suggesting that NP sequestration into VCC has additional requirements beyond ligand (GM3)-receptor (CD169) recognition that are related to the physical properties of the NP core. Our results confirm AVN as a scalable platform for elucidating the mechanisms of lipid-mediated viral entry pathways and for selective intracellular targeting., Competing Interests: Conflict of interest statement: S.G. and B.M.R. have filed a patent for GM3-functionalized nanoparticles.

We demonstrate a novel approach for fabricating surface enhanced Raman scattering (SERS) substrates for single bacterial biosensing based on Ag cylindrical nanotrough networks (CNNs). This approach is developed with large scalability by leveraging a cellulose nanofiber template fabrication via facile electrospinning. Specifically, a concave nanotrough structure consisting of interconnected concave Ag nanoshells is demonstrated by depositing a thin layer of Ag atop a sacrificial electrospun nanofiber template and then completely removing the cellulose core in water. Our investigations of the scattering properties and SERS performances of single isolated Ag nanotroughs of different diameters reveal that nanotrough-based substrates provide tunable optical responses and enhanced SERS intensities. Further, Ag CNNs are fabricated in highly interconnected networks that yield reproducible SERS signals for molecular monolayers and whole bacterial cells, enabling rapid spectral discrimination between different bacterial strains. Finally, by performing principal component analysis on a large number of measured SERS spectra (40 spectra per bacterium), we demonstrate successful spectral discrimination between two types of Escherichia coli ( E. coli) bacteria, that is, E. coli K12 with its derivative E. coli DH 5α and E. coli BL21(DE3). The demonstrated cost-effective substrates feature several advantages over conventional SERS substrates including environmentally friendly and scalable fabrication compatible with versatile devices and provide an alternative approach to rapid SERS detection and screening of biochemicals.

Capacitive plasmon coupling between noble metal nanoparticles (NPs) is characterized by an increasing red-shift of the bonding dipolar plasmon mode (BDP) in the classical electromagnetic coupling regime. This model breaks down at short separations where plasmon-driven charge transfer induces a gap current between the NPs with a magnitude and separation dependence that can be modulated if molecules are present in the gap. Here, we use gap contained DNA as a scaffold for the growth of palladium (Pd) NPs in the gap between two gold NPs and investigate the effect of increasing Pd NP concentration on the BDP mode. Consistent with enhanced plasmon-driven charge transfer, the integration of discrete Pd NPs depolarizes the capacitive BDP mode over longer interparticle separations than is possible in only DNA-linked Au NPs. High Pd NP densities in the gap increases the gap conductance and induces the transition from capacitive to conductive coupling.

In addition to the intrinsic toxicity associated with the chemical composition of nanoparticles (NP) and their ligands, biofunctionalized NP can perturb specific cellular processes through NP-cell interactions and induce programmed cell death (apoptosis). In the case of the epidermal growth factor (EGF), nanoconjugation has been shown to enhance the apoptotic efficacy of the ligand, but the critical aspects of the underlying mechanism and its dependence on the NP morphology remain unclear. In this manuscript we characterize the apoptotic efficacy of nanoconjugated EGF as a function of NP size (with sphere diameters in the range 20-80 nm), aspect ratio (A.R., in the range of 4.5 to 8.6), and EGF surface loading in EGFR overexpressing MDA-MB-468 cells. We demonstrate a significant size and morphology dependence in this relatively narrow parameter space with spherical NP with a diameter of approx. 80 nm being much more efficient in inducing apoptosis than smaller spherical NP or rod-shaped NP with comparable EGF loading. The nanoconjugated EGF is found to trigger an EGFR-dependent increase in cytoplasmic reactive oxygen species (ROS) levels but no indications of increased mitochondrial ROS levels or mitochondrial membrane damage are detected at early time points of the apoptosis induction. The increase in cytoplasmic ROS is accompanied by a perturbation of the intracellular glutathione homeostasis, which represents an important check-point for NP-EGF mediated apoptosis. Abrogation of the oxidative stress through the inhibition of EGFR signaling by the EGFR inhibitor AG1478 or addition of antioxidants N-acetyl cysteine (NAC) or tempol, but not trolox, successfully suppressed the apoptotic effect of nanoconjugated EGF. A model to account for the observed morphology dependence of EGF nanoconjugation enhanced apoptosis and the underlying NP-cell interactions is discussed.

Sn-doped indium oxide (ITO) nanocrystals (NC) provide tunable localized surface plasmon resonance in the mid-infrared. To evaluate the applicability of these n-doped plasmonic semiconductors in field-enhanced spectroscopies, it is necessary to assess how the low, free-electron density affects the E-field localization and plasmon coupling in NC films when compared to metal nanoparticles (NP). In this article, we investigate plasmon coupling between approximate 6 nm diameter ITO NC on the collective resonance and quantify the effect of the electromagnetic field enhancement on the absorbance signal of surface-attached ligands in NC films and monolayers with different ratios of doped and undoped indium oxide NC., Competing Interests: The authors declare no competing financial interest.

Viral membranes are nanomaterials whose fluidity depends on their composition, in particular, the cholesterol (chol) content. As differences in the membrane composition of individual virus particles can lead to different intracellular fates, biophysical tools capable of sensing the membrane fluidity on the single-virus level are required. In this manuscript, we demonstrate that fluctuations in the polarization of light scattered off gold or silver nanoparticle (NP)-labeled virus-like-particles (VLPs) encode information about the membrane fluidity of individual VLPs. We developed plasmonic polarization fluctuation tracking microscopy (PFTM) which facilitated the investigation of the effect of chol content on the membrane fluidity and its dependence on temperature, for the first time on the single-VLP level. Chol extraction studies with different methyl-β-cyclodextrin (MβCD) concentrations yielded a gradual decrease in polarization fluctuations as a function of time. The rate of chol extraction for individual VLPs showed a broad spread, presumably due to differences in the membrane composition for the individual VLPs, and this heterogeneity increased with decreasing MβCD concentration.

Self-assembly of functionalized nanoparticles (NPs) provides a unique class of nanomaterials for exploring and utilizing quantum-plasmonic effects that occur if the interparticle separation between NPs approaches a few nanometers and below. We review recent theoretical and experimental studies of plasmon coupling in self-assembled NP structures that contain molecular linkers between the NPs. Charge transfer through the interparticle gap of an NP dimer results in a significant blue-shift of the bonding dipolar plasmon (BDP) mode relative to classical electromagnetic predictions, and gives rise to new coupled plasmon modes, the so-called charge transfer plasmon (CTP) modes. The blue-shift of the plasmon spectrum is accompanied by a weakening of the electromagnetic field in the gap of the NPs. Due to an optical far-field signature that is sensitive to charge transfer across the gap, plasmonic molecules represent a sensor platform for detecting and characterizing gap conductivity in an optical fashion and for characterizing the role of molecules in facilitating the charge transfer across the gap.

Femtosecond (fs) pulsed laser irradiation techniques have attracted interest as a photonic approach for the selective inactivation of virus contaminations in biological samples. Conventional pulsed laser approaches require, however, relatively long irradiation times to achieve a significant inactivation of virus. In this study, we investigate the enhancement of the photonic inactivation of Murine Leukemia Virus (MLV) via 805 nm femtosecond pulses through gold nanorods whose localized surface plasmon resonance overlaps with the excitation laser. We report a plasmonically enhanced virus inactivation, with greater than 3.7-log reduction measured by virus infectivity assays. Reliable virus inactivation was obtained for 10 s laser exposure with incident laser powers ≥0.3 W. Importantly, the fs-pulse induced inactivation was selective to the virus and did not induce any measurable damage to co-incubated antibodies. The loss in viral infection was associated with reduced viral fusion, linking the loss in infectivity with a perturbation of the viral envelope. Based on the observations that physical contact between nanorods and virus particles was not required for viral inactivation and that reactive oxygen species (ROS) did not participate in the detected viral inactivation, a model of virus inactivation based on plasmon enhanced shockwave generation is proposed.

The development of optical materials and devices that mimic the functionalities of conventional bulky optical components but on a much smaller footprint remains an important priority in nanophotonics. One prominent class of such optical elements are polarizers that change the polarization state of incident light. Recently, advances in plasmonic and photonic metasurfaces have given rise to different classes of subwavelength polarizers. Low efficiency and narrow band of operation remain, however, significant challenges. Here, we propose a device based on high refractive index dielectric nanowire dimers and analyze its working mechanism as efficient and broadband circular polarizers in the optical region of the electromagnetic spectrum. Our analysis predicts that a polarization conversion of roughly 97% with a transmission efficiency of more than 93% in a broad range of the visible spectrum is possible with nanowire dimers.

Sensors are devices or systems able to detect, measure and convert magnitudes from any domain to an electrical one. Using light as a probe for optical sensing is one of the most efficient approaches for this purpose. The history of optical sensing using some methods based on absorbance, emissive and florescence properties date back to the 16th century. The field of optical sensors evolved during the following centuries, but it did not achieve maturity until the demonstration of the first laser in 1960. The unique properties of laser light become particularly important in the case of laser-based sensors, whose operation is entirely based upon the direct detection of laser light itself, without relying on any additional mediating device. However, compared with freely propagating light beams, artificially engineered optical fields are in increasing demand for probing samples with very small sizes and/or weak light-matter interaction. Optical fiber sensors constitute a subarea of optical sensors in which fiber technologies are employed. Different types of specialty and photonic crystal fibers provide improved performance and novel sensing concepts. Actually, structurization with wavelength or subwavelength feature size appears as the most efficient way to enhance sensor sensitivity and its detection limit. This leads to the area of micro- and nano-engineered optical sensors. It is expected that the combination of better fabrication techniques and new physical effects may open new and fascinating opportunities in this area. This roadmap on optical sensors addresses different technologies and application areas of the field. Fourteen contributions authored by experts from both industry and academia provide insights into the current state-of-the-art and the challenges faced by researchers currently. Two sections of this paper provide an overview of laser-based and frequency comb-based sensors. Three sections address the area of optical fiber sensors, encompassing both conventional, specialty and photonic crystal fibers. Several other sections are dedicated to micro- and nano-engineered sensors, including whispering-gallery mode and plasmonic sensors. The uses of optical sensors in chemical, biological and biomedical areas are described in other sections. Different approaches required to satisfy applications at visible, infrared and THz spectral regions are also discussed. Advances in science and technology required to meet challenges faced in each of these areas are addressed, together with suggestions on how the field could evolve in the near future.

The encapsulation of individual pairs of plasmonic nanoparticles (NPs) in liposomes is introduced as a new strategy for utilizing plasmon coupling to monitor interactions between co-confined NPs in a nanoconfinement that ensures high local NP concentrations. We apply the approach to monitor transient binding contacts between noncovalently tethered 55 nm diameter gold NPs, which were functionalized with cytosine (C)-rich DNAs, in acidic and mildly basic buffer conditions. At pH = 8, a rich spectral dynamics indicates DNA-mediated transient binding and unbinding of co-confined NPs due to weak attractive interparticle interactions. A decrease in pH from 8 to 4 is observed to favor the associated state for some co-confined NPs, presumably due to a stabilization of the bound dimer configuration through noncanonical C-C + bonds between the DNA-functionalized NPs. Plasmonic nanoemitters whose spectral response switches in response to chemical cues (in this work pH) represent optical transducers with a rich application space in chemical sensing, cell analysis and nanophotonics., Competing Interests: COMPETING INTERESTS The authors declare no conflict of interest.

Transverse spin angular momentum (SAM) of light and associated transverse chiral optical forces have received tremendous attention recently, as the latter may lead to an optical separation of chiral biomolecules. In this context, the relative magnitude of chiral and non-chiral forces is a challenge when implementing chiral separation schemes. In this work we have demonstrated that, by spatially separating the maxima of transverse spin density from the gradient of field intensity, it is possible to dominate chiral-specific components of the force over non-chiral ones. To that end, we studied optical nanofibers and nanowires as candidates for such a scheme and demonstrated that in their vicinity, chiral optical forces can emerge that are stronger than gradient and scattering forces. This finding may be of significance in the design of improved optical separation schemes for chiral biomolecules.

The mechanisms behind the low viral loads and lower mortality rates of HIV-2(+) individuals remain unknown. We hypothesized that reduced interaction of HIV-2 with CD169, the primary HIV-1 attachment factor on monocyte-derived dendritic cells (DCs) that targets captured virus particles to the trans infection pathway, contributes to its diminished pathogenic phenotype in vivo. We observed a significant decrease in capture of HIV-2 Gag-eGFP virus-like particles (VLPs) and infectious GFP-containing HIV-2 particles compared to corresponding HIV-1 particles by CD169(+) mature DCs. Interestingly, there was decreased co-localization of HIV-2 with HIV-1 Gag at plasma membrane microdomains in virus producer cells which correlated with reduced incorporation of GM3, the CD169 ligand, in HIV-2 virions, and reduction in mature DC-mediated HIV-2 trans infection compared to HIV-1. We conclude that limited interaction of HIV-2 with CD169 diminishes virus access to the mature DC-mediated trans infection pathway and might result in attenuated HIV-2 dissemination in vivo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hybrid structures containing plasmonic and photonic components can enhance light-matter interaction through both photonic and plasmonic modes and potentially their interactions. In this article, we systematically investigate the optical properties of nanoparticle-tipped silicon nanowires (NPTWs) and characterize their ability to enhance the fluorescence signal of two cyanine dyes (Cy3 and Cy5) selectively bound to the gold tip. Although both gold and silicon components contribute to the fluorescence signal enhancement, the experimentally observed strong morphology dependence of the fluorescence emission enhancement is demonstrated to depend on tunable leaky modes of the silicon nanowires. The ability to encode emission fluorescence enhancement in the structure of NPTWs is of high relevance for multiparametric biosensing and imaging., Competing Interests: The authors declare no competing financial interest.

It is becoming increasingly clear that intracellular signaling can be subject to strict spatial control. As the covalent attachment of a signaling ligand to a nanoparticle (NP) impacts ligand-receptor binding, uptake, and trafficking, nanoconjugation provides new opportunities for manipulating intracellular signaling in a controlled fashion. To establish the effect of nanoconjugation on epidermal growth factor (EGF) mediated signaling, we investigate here the intracellular fate of nanoconjugated EGF (NP-EGF) and its bound receptor (EGFR) by quantitative correlated darkfield/fluorescence microscopy and density-based endosomal fractionation. We demonstrate that nanoconjugation prolongs the dwell time of phosphorylated receptors in the early endosomes and that the retention of activated EGFR in the early endosomes is accompanied by an EGF mediated apoptosis at effective concentrations that do not induce apoptosis in the case of free EGF. Overall, these findings indicate nanoconjugation as a rational strategy for modifying signaling that acts by modulating the temporo-spatial distribution of the activated EGF-EGFR ligand-receptor complex.

Nanoparticles of different materials, shapes, and sizes are integrated into plasmonic atoms and molecules of defined shape and location through sequential directed self-assembly following a single patterning step. A rational tuning of the emitted color across the visible range of the electromagnetic spectrum and switchable polarization properties are demonstrated. Self-assembled plasmonic pixels provide tunable, stable, and switchable optical responses., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The transverse spin angular momentum of light has recently received tremendous attention as it adds a new degree of freedom for controlling light-matter interactions. In this work we demonstrate the generation of transverse spin angular momentum by the weakly-guided mode of semiconductor nanowires. The evanescent field of these modes in combination with the transversality condition rigorously accounts for the occurrence of transverse spin angular momentum. The intriguing and nontrivial spin properties of optical modes in semiconductor nanowires are of high interest for a broad range of new applications including chiral optical trapping, quantum information processing, and nanophotonic circuitry.

Plasmon coupling between DNA-tethered gold nanoparticles is investigated by correlated single-particle spectroscopy and transmission electron microscopy for interparticle separations between 0.5 and 41 nm. Spectral characterization reveals a weakening of the plasmon coupling due to DNA-mediated charge transfer for separations up to 2.8 nm. Electromagnetic simulations indicate a coherent charge transfer across the DNA., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Optoplasmonic structures contain plasmonic components embedded in a defined photonic environment to create synergistic interactions between photonic and plasmonic components. Here, we show that chains of optical microspheres containing gold nanoparticles in their evanescent field combine the light guiding properties of a microsphere chain with the light localizing properties of a plasmonic nanoantenna. We implement these materials through template guided self-assembly and investigate their fundamental electromagnetic working principles through combination of electromagnetic simulations and experimental characterization. We demonstrate that optoplasmonic chains implemented by directed self-assembly achieve a significant reduction in guiding losses when compared with conventional plasmonic waveguides and, at the same time, retain the light localizing properties of plasmonic antennas at pre-defined locations. The results reinforce the potential of optoplasmonic structures for realizing low-loss optical interconnects with high bandwidth.

Membrane-wrapped nanoparticles represent a versatile platform for utilizing specific lipid-receptor interactions, such as siallyllactose-mediated binding of the ganglioside GM3 to Siglec1 (CD169), for targeting purposes. The membrane wrap around the nanoparticles not only serves as a matrix to incorporate GM3 as targeting moiety for antigen-presenting cells but also offers unique opportunities for constructing a biomimetic surface from lipids with potentially protein-repellent properties. We characterize nonspecific protein adsorption (corona formation) to membrane-wrapped nanoparticles with core diameters of approximately 35 and 80 nm and its effect on the GM3-mediated targeting efficacy as a function of surface charge through combined in vitro and in vivo studies. The stability and fate of the membrane wrap around the nanoparticles in a simulated biological fluid and after uptake in CD169-expressing antigen-presenting cells is experimentally tested. Finally, we demonstrate in hock immunization studies in mice that GM3-decorated membrane-wrapped nanoparticles achieve a selective enrichment in the peripheral regions of popliteal lymph nodes that contain high concentrations of CD169-expressing antigen-presenting cells.

Unlabelled: Basal-like breast cancer (BLBC) is an aggressive subtype of breast cancer which is often enriched with cancer stem cells (CSC), but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin α(v)β(3), are highly expressed in a subset of BLBC cell lines as well as in CSC-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin β3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-κB-mediated transcription of key cytokines, namely IL6 and IL8, which in turn control downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs., Implications: The findings reported here indicate that POSTN produced by CSCs acts to reinforce the stem cell state through the activation of integrin receptors and the production of key cytokines., (©2015 American Association for Cancer Research.)

The distance-dependent plasmon coupling between biopolymer tethered gold or silver nanoparticles forms the foundation for the so-called plasmon rulers. While conventional plasmon ruler applications focus on the detection of singular events in the far-field spectrum, we perform in this Letter a ratiometric analysis of the continuous spectral fluctuations arising from thermal interparticle separation variations in plasmon rulers confined to fluid lipid membranes. We characterized plasmon rulers with different DNA tethers and demonstrate the ability to detect and quantify differences in the plasmon ruler potential and tether stiffness. The influence of the nature of the tether (single-stranded versus double-stranded DNA) and the length of the tether is analyzed. The characterization of the continuous variation of the interparticle separation in individual plasmon rulers through optical fluctuation analysis provides additional information about the conformational flexibility of the tether molecule(s) located in the confinement of the deeply subdiffraction limit interparticle gap and enhances the versatility of plasmon rulers as a tool in Biophysics and Nanotechnology.

Optoplasmonic materials are metallo-dielectric hybrid structures that combine metallic and dielectric components in defined geometries in which plasmonic and photonic modes synergistically interact. These beneficial interactions can be harnessed by integrating plasmonic nanoantennas into defined photonic environments generated, for instance, by discrete optical resonators or extended systems of diffractively coupled nanoparticles. Optoplasmonic structures facilitate photonic-plasmonic mode coupling and offer degrees of freedom for creating optical fields with predefined amplitude and phase in space and time that are absent in conventional photonic or plasmonic structures. This Perspective reviews the fundamental electromagnetic mechanisms underlying selected optoplasmonic approaches with an emphasis on materials available through template-guided self-assembly strategies.

Phosphatidylserine (PS) and monosialotetrahexosylganglioside (GM1 ) are examples of two host-derived lipids in the membrane of enveloped virus particles that are known to contribute to virus attachment, uptake, and ultimately dissemination. A quantitative characterization of their contribution to the functionality of the virus requires information about their relative concentrations in the viral membrane. Here, a gold nanoparticle (NP) binding assay for probing relative PS and GM1 lipid concentrations in the outer leaflet of different HIV-1 and Ebola virus-like particles (VLPs) using sample sizes of less than 3 × 10(6) particles is introduced. The assay evaluates both scattering intensity and resonance wavelength, and determines relative NP densities through plasmon coupling as a measure for the target lipid concentrations in the NP-labeled VLP membrane. A correlation of the optical observables with absolute lipid contents is achieved by calibration of the plasmon coupling-based methodology with unilamellar liposomes of known PS or GM1 concentration. The performed studies reveal significant differences in the membrane of VLPs that assemble at different intracellular sites and pave the way to an optical quantification of lipid concentration in virus particles at physiological titers., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel fiber optical refractive index sensor based on gold nanoshells immobilized on the surface of an etched single-mode fiber including a Bragg grating is demonstrated. The nanoparticle coating induces refractive index dependent waveguide losses, because of the variation of the evanescently guided part of the light. Hence the amplitude of the Bragg reflection is highly sensitive to refractive index changes of the surrounding medium. The nanoshell functionalized fiber optical refractive index sensor works in reflectance mode, is suitable for chemical and biochemical sensing, and shows an intensity dependency of 4400% per refractive index unit in the refractive index range between 1.333 and 1.346. Furthermore, the physical length of the sensor is smaller than 3 mm with a diameter of 6 μm, and therefore offers the possibility of a localized refractive index measurement.