Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

The role of peptides in the design of electrochemical biosensors for clinical diagnostics

Peptides represent a promising class of biorecognition elements that can be coupled to electrochemical transducers. The benefits lie mainly in their stability and selectivity toward a target analyte. Furthermore, they can be synthesized rather easily and modified with specific functional groups, thus making them suitable for the development of novel architectures for biosensing platforms, as well as alternative labelling tools. Peptides have also been proposed as antibiofouling agents. Indeed, biofouling caused by the accumulation of biomolecules on electrode surfaces is one of the major issues and challenges to be addressed in the practical application of electrochemical biosensors. In this review, we summarise trends from the last three years in the design and development of electrochemical biosensors using synthetic peptides. The different roles of peptides in the design of electrochemical biosensors are described. The main procedures of selection and synthesis are discussed. Selected applications in clinical diagnostics are also described

The role of peptides in the design of electrochemical biosensors for clinical diagnostics

Peptides represent a promising class of biorecognition elements that can be coupled to electrochemical transducers. The benefits lie mainly in their stability and selectivity toward a target analyte. Furthermore, they can be synthesized rather easily and modified with specific functional groups, thus making them suitable for the development of novel architectures for biosensing platforms, as well as alternative labelling tools. Peptides have also been proposed as antibiofouling agents. Indeed, biofouling caused by the accumulation of biomolecules on electrode surfaces is one of the major issues and challenges to be addressed in the practical application of electrochemical biosensors. In this review, we summarise trends from the last three years in the design and development of electrochemical biosensors using synthetic peptides. The different roles of peptides in the design of electrochemical biosensors are described. The main procedures of selection and synthesis are discussed. Selected applications in clinical diagnostics are also described

Measurement of the water vapour vertical profile and of the Earth's outgoing far infrared flux

International audienceOur understanding of global warming depends on the accuracy with which the atmospheric components that modulate the Earth's radiation budget are known. Many uncertainties still exist on the radiative effect of water in the different spectral regions, among which the far infrared where few observations have been made. An assessment is shown of the atmospheric outgoing flux obtained from a balloon-borne platform with wideband spectrally resolved nadir measurements at the top-of-atmosphere over the full spectral range, including the far infrared, from 100 to 1400 cm?1, made by a Fourier transform spectrometer with uncooled detectors. From these measurements, we retrieve 15 pieces of information about water vapour and temperature profiles, and surface temperature, with a precision of 5% for the mean water vapour profile and a major improvement of the upper troposphere-lower stratosphere knowledge. The retrieved atmospheric state makes it possible to calculate the emitted radiance as a function of the zenith angle and to determine the outgoing radiation flux, proving that spectrally resolved observations can be used to derive accurate information on the integrated flux. While the retrieved temperature is in good agreement with ECMWF analysis, the retrieved water vapour profile differs significantly, and, depending on time and location, the derived flux differs in the far infrared (0?600 cm?1) from that derived from ECMWF by 2?3.5 W/m2±0.4 W/m2. The observed discrepancy is larger than current estimates of radiative forcing due to CO2 increases since pre-industrial time. The error with which the flux is determined is caused mainly by calibration uncertainties while detector noise has a negligible effect, proving that uncooled detectors are adequate for top of the atmosphere radiometry

Stimulation of Ca2+-ATPase Transport Activity by a Small-Molecule Drug

The sarco(endo)plasmic reticulum Ca(2+)−ATPase (SERCA) hydrolyzes ATP to transport Ca(2+) from the cytoplasm to the sarcoplasmic reticulum (SR) lumen, thereby inducing muscle relaxation. Dysfunctional SERCA has been related to various diseases. The identification of small‐molecule drugs that can activate SERCA may offer a therapeutic approach to treat pathologies connected with SERCA malfunction. Herein, we propose a method to study the mechanism of interaction between SERCA and novel SERCA activators, i. e. CDN1163, using a solid supported membrane (SSM) biosensing approach. Native SR vesicles or reconstituted proteoliposomes containing SERCA were adsorbed on the SSM and activated by ATP concentration jumps. We observed that CDN1163 reversibly interacts with SERCA and enhances ATP‐dependent Ca(2+) translocation. The concentration dependence of the CDN1163 effect provided an EC(50)=6.0±0.3 μM. CDN1163 was shown to act directly on SERCA and to exert its stimulatory effect under physiological Ca(2+) concentrations. These results suggest that CDN1163 interaction with SERCA can promote a protein conformational state that favors Ca(2+) release into the SR lumen

Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid

In this work a novel self-powered microneedle-based transdermal biosensor for pain-free high-accuracy real-time measurement of glycaemia in interstitial fluid (ISF) is reported. The proposed transdermal biosensor makes use of an array of silicon-dioxide hollow microneedles that are about one order of magnitude both smaller (borehole down to 4 µm) and more densely-packed (up to 1×106 needles/cm2) than state-of-the-art microneedles used for biosensing so far. This allows self-powered (i.e. pump-free) uptake of ISF to be carried out with high efficacy and reliability in a few seconds (uptake rate up to 1 µl/s) by exploiting capillarity in the microneedles. By coupling the microneedles operating under capillary-action with an enzymatic glucose biosensor integrated on the back-side of the needle-chip, glucose measurements are performed with high accuracy (±20% of the actual glucose level for 96% of measures) and reproducibility (coefficient of variation 8.56%) in real-time (30 s) over the range 0–630 mg/dl, thus significantly improving microneedle-based biosensor performance with respect to the state-of-the-art

Comparison of mid-latitude single- And mixed-phase cloud optical depth from co-located infrared spectrometer and backscatter lidar measurements

The long-wave downwelling spectral radiance measurements performed by means of the Far-Infrared Radiation Mobile Observation System (FIRMOS) spectrometer at the summit of the Zugspitze (German Alps) in the winter 2018/19 allowed the retrieval of the optical and micro-physical properties of ice and mixed clouds, showing a good agreement of the statistical relationship between the ice water path and the ice optical depth with the ones from previous works. In this paper the optical depths retrieved from FIRMOS are initially compared with selected cases calculated from backscattering light detection and ranging (lidar) data by using a transmittance method. Then, in order to compare the whole FIRMOS dataset, the power-law relationship between backscattering and extinction is used to apply the Klett method and automatize the routine. Minimizing the root mean square differences, the exponent k of the power-law relationship is assessed to be 0.85 with a variability in the range of 0.60–1.10 for ice clouds and 0.50 with a variability within 0.30–0.70 for mixed clouds