4 research outputs found
Size and Surface Functionalization of Iron Oxide Nanoparticles Influence the Composition and Dynamic Nature of Their Protein Corona
Nanoparticles (NPs) adsorb proteins
when in the biological matrix, and the resulted protein corona could
affect NP-cell interactions. The corona has a dynamic nature with
the adsorbed proteins constantly exchanging with the free proteins
in the matrix at various rates. The rapidly exchanging proteins compose
the soft corona, which responds more dynamically to environment changes
than the hard corona established by the ones with slow exchange rates.
In the present study, the corona formed on the superparamagnetic iron
oxide NPs (SPIONs) in human serum was studied by flow field-flow fractionation
and ultracentrifugation, which rapidly differentiated the corona proteins
based on their exchange rates. By varying the surface hydrophobicity
of the SPIONs with a core size around 10 nm, we found out that, the
more hydrophobic surface ligand attracted proteins with higher surface
hydrophobicity and formed a more dynamic corona with a larger portion
of the involved proteins with fast exchange rates. Increasing the
core diameter of the SPIONs but keeping the surface ligand the same
could also result in a more dynamic corona. A brief investigation
of the effect on the cellular uptake of SPIONs using one selected
corona protein, transferrin, was conducted. The result showed that,
only the stably bound transferrin could significantly enhance cellular
uptake, while transferrin bound in a dynamic nature had negligible
impact. Our study has led to a better understanding of the relationship
between the particle properties and the dynamic nature of the corona,
which can help with design of nanomaterials with higher biocompatibility
and higher efficacy in biosystems for biomedical applications
Dissociation-Based Screening of Nanoparticle–Protein Interaction via Flow Field-Flow Fractionation
A protein
corona will be formed on nanoparticles (NPs) entering a biological
matrix, which can influence particles’ subsequent behaviors
inside the biological systems. For proteins bound stably to the NPs,
they can exhibit different association/dissociation rates. The binding
kinetics could affect interaction of the NPs with cell surface receptors
and possibly contribute to the outcomes of NPs uptake. In the present
study, a method to differentiate the corona proteins based on their
relative dissociation rates from the NPs was developed, employing
flow field-flow fraction (F4) in combination with centrifugation.
The proteins bound to the superparamagnetic iron oxide NPs (SPION)
present in an IgG/albumin depleted serum were isolated via collection
of the SPIONs by either F4 or centrifugation. They were subsequently
analyzed by LC-MS/MS and identified. Because the SPION-protein complexes
injected to F4 dissociated continuously under the nonequilibrium separation
condition, only the proteins with slow enough dissociation rates would
be collected with the NPs in the eluent of F4. However, in centrifugation,
proteins with good affinity to the SPIONs were collected regardless
of the dissociation rates of the complexes. In both cases, the nonbinding
ones were washed off. Capillary electrophoresis and circular dichroism
were employed to verify the binding situations of a few SPION-protein
interactions, confirming the effectiveness of our method. Our results
support that our method can screen for proteins binding to NPs with
fast on-and-off rates, which should be the ones quickly exchanging
with the free matrix proteins when the NPs are exposed to a new biological
media. Thus, our method will be useful for investigation of the temporal
profile of protein corona and its evolution in biological matrices
as well as for high-throughput analysis of the dynamic feature of
protein corona related to particle properties
Histoire d'une faculté sous le prisme de la dérision étudiante
L'ouvrage est une analyse des textes des dix revues satiriques produites par le Cercle des étudiants en médecine de l'Université libre de Bruxelles de 1944 à 2014.Le parti a été pris de considérer ces revues comme un témoignage du regard que les étudiants d'une époque donnée ont porté sur leur professeurs, leur faculté, leur hôpitaux de stages et, d'une manière plus générale, sur leur environnement social et politique.L'analyse des revues est ainsi un moyen de suivre l'actualité de la faculté de médecine et de ses hôpitaux, en tous cas, celle qui a frappé les étudiants.Elle permet aussi d'identifier les quelques personnalités qui, aux yeux des étudiants, ont marqué le vie de la faculté, soit par leur côté particulièrement caricatural, soit par leur rôle politique et de ressentir la perception par les étudiants de ce que fut pour eux les problématiques les plus critiques.info:eu-repo/semantics/publishe
Proteomic Analysis of Endothelial Lipid Rafts Reveals a Novel Role of Statins in Antioxidation
As inhibitors of 3-hydroxy-3-methylglutaryl coenzyme
A reductase,
statins have pleiotropic vascular-protective effects, such as anti-inflammatory
and antioxidative effects. We investigated the short-term beneficial
effects of statins on modulating the translocation of lipid-raft-related
proteins in endothelial cells (ECs). Human umbilical vein ECs were
treated with atorvastatin for 30 min or 2 h; lipid-raft proteins were
isolated and examined by quantitative proteome assay. Functional classification
of identified proteins in lipid rafts revealed upregulated antioxidative
proteins; downregulated proteins were associated with inflammation
and cell adhesion. Among proteins verified by Western blot analysis,
endoplasmic reticulum protein 46 (ERp46) showed increased level in
lipid rafts with atorvastatin. Further, atorvastatin inhibited the
activation of membrane-bound NADPH oxidase in both untreated and angiotensin
II-treated ECs, as shown by reduced reactive oxygen species production.
Co-immunoprecipitation and immunofluorescence experiments revealed
that atorvastatin increased the association of ERp46 and Nox2, an
NADPH oxidase isoform, in lipid rafts, thereby inhibiting Nox2 assembly
with its regulatory subunits, such as p47phox and p67phox. Our results
reveal a novel antioxidative role of atorvastatin by promoting the
membrane translocation of ERp46 and its binding with Nox2 to inhibit
Nox2 activity in ECs, which may offer another insight into the pleiotropic
functions of statins