Multicolor Super-Resolution Microscopy of Protein Corona on Single Nanoparticles

Nanoparticles represent a promising class of material for nanomedicine and molecular biosensing. The formation of a protein corona due to nonspecific particle-protein interactions is a determining factor for the biological fate of nanoparticles in vivo and strongly impacts the performance of nanoparticles when used as biosensors. Nonspecific interactions are usually highly heterogeneous, yet little is known about the heterogeneity of the protein corona that may lead to inter- and intraparticle differences in composition and protein distribution. Here, we present a super-resolution microscopic approach to study the protein corona on single silica nanoparticles and subsequent cellular interactions using multicolor stimulated emission depletion (STED) microscopy. We demonstrate that STED resolves structural features of protein corona on single particles including the distribution on the particle surface and the degree of protein internalization in porous particles. Using multicolor measurements of multiple labeled protein species, we determine the composition of the protein corona at the single-particle level. We quantify particle-to-particle differences in the composition and find that the composition is considerably influenced by the particle geometry. In a subsequent cellular uptake measurement, we demonstrate multicolor STED of protein corona on single particles internalized by cells. Our study shows that STED microscopy opens the window toward mechanistic understanding of protein coronas and aids in the rational design of nanoparticles as nanomedicines and biosensors

Real-time Optical Tracking of Protein Corona Formation on Single Nanoparticles in Serum

Significant advances in synthesis and functionalization have provided state-of-the-art technology in controlling the physico-chemical properties of nanomaterials. These are finding numerous applications including in the biomedical field whereby nanoparticles are injected in vivo for medical imaging, theranostics and biosensing. However, interactions with proteins contained in biological fluids lead to the formation of a shell on the surface of the nanoparticles called "protein corona" (PC). PC plays a detrimental role for the intended applications as it may modify the interface of the nanoparticle and thereby block functional groups needed for recognition. It is therefore essential to understand the mechanisms of formation of these PCs in order to control the surface chemistry of the nanoparticles in complex biological fluids. Current characterization techniques can identify and quantify the composition of PCs using mass spectroscopy and electrophoresis. However, most of them do not enable real-time measurement in complex media because they require washing steps to remove excess protein. Finally, most techniques provide ensemble averages and are unable to access inter-particle heterogeneity. Here, we demonstrate the use of single-particle scattering microscopy combined with a microfluidic system to study PC formation in real-time at the single-nanoparticle level. The method is label-free and operates in undiluted blood serum. We probe PC formation on both, metallic and dielectric nanoparticles with different surface chemistries. Analysis of protein adsorption revealed unexpectedly strong heterogeneity whereby the amount of accumulated protein varies by up to a factor of 10 between the particles. Furthermore, it is found that the surface roughness of the nanoparticles affects the kinetics of the PC formation. The results of this in-situ characterization are a powerful tool to optimize the surface chemistry in order to minimize the formation of PCs and thus increase the efficiency of nanoparticles for applications such as targeted drug delivery

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

DUNE Offline Computing Conceptual Design Report

International audienceThis document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

Exclusive and dissociative <math display="inline"><mi>J</mi><mo>/</mo><mi>ψ</mi></math> photoproduction, and exclusive dimuon production, in p-Pb collisions at <math display="inline"><mrow><msqrt><mrow><msub><mrow><mi>s</mi></mrow><mrow><mi>NN</mi></mrow></msub></mrow></msqrt><mo>=</mo><mn>8.16</mn><mtext> </mtext><mtext> </mtext><mi>TeV</mi></mrow></math>

International audienceThe ALICE Collaboration reports three measurements in ultraperipheral proton-lead collisions at forward rapidity. The exclusive two-photon process γγ→μ+μ- and the exclusive photoproduction of J/ψ are studied. J/ψ photoproduction with proton dissociation is measured for the first time at a hadron collider. The cross section for the two-photon process of dimuons in the invariant mass range from 1 to 2.5  GeV/c2 agrees with leading-order quantum electrodynamics calculations. The exclusive and dissociative cross sections for J/ψ photoproductions are measured for photon-proton center-of-mass energies from 27 to 57 GeV. They are in good agreement with HERA results

Skewness and kurtosis of mean transverse momentum fluctuations at the LHC energies

The first measurements of skewness and kurtosis of mean transverse momentum (〈pT〉) fluctuations are reported in Pb–Pb collisions at sNN = 5.02 TeV, Xe–Xe collisions at sNN = 5.44 TeV and pp collisions at s=5.02 TeV using the ALICE detector. The measurements are carried out as a function of system size 〈dNch/dη〉|η|<0.51/3, using charged particles with transverse momentum (pT) and pseudorapidity (η), in the range 0.2<pT<3.0 GeV/c and |η|<0.8, respectively. In Pb–Pb and Xe–Xe collisions, positive skewness is observed in the fluctuations of 〈pT〉 for all centralities, which is significantly larger than what would be expected in the scenario of independent particle emission. This positive skewness is considered a crucial consequence of the hydrodynamic evolution of the hot and dense nuclear matter created in heavy-ion collisions. Furthermore, similar observations of positive skewness for minimum bias pp collisions are also reported here. Kurtosis of 〈pT〉 fluctuations is found to be in good agreement with the kurtosis of Gaussian distribution, for most central Pb–Pb collisions. Hydrodynamic model calculations with MUSIC using Monte Carlo Glauber initial conditions are able to explain the measurements of both skewness and kurtosis qualitatively from semicentral to central collisions in Pb–Pb system. Color reconnection mechanism in PYTHIA8 model seems to play a pivotal role in capturing the qualitative behavior of the same measurements in pp collisions