Protein nanoparticles are nontoxic, tuneable cell stressors Aim: Nanoparticle–cell interactions can promote cell toxicity and stimulate particular behavioral patterns, but cell responses to protein nanomaterials have been poorly studied. Results: By repositioning oligomerization domains in a simple, modular self-assembling protein platform, we have generated closely related but distinguishable homomeric nanoparticles. Composed by building blocks with modular domains arranged in different order, they share amino acid composition. These materials, once exposed to cultured cells, are differentially internalized in absence of toxicity and trigger distinctive cell adaptive responses, monitored by the emission of tubular filopodia and enhanced drug sensitivity. Conc
Improving biomaterials imaging for nanotechnology: rapid methods for protein localization at ultrastructural level http://onlinelibrary.wiley.com/doi/10.1002/biot.201700388/full Abstract The preparation of biological samples for electron microscopy is material- and time-consuming because it is often based on long protocols that also may produce artifacts. Protein labeling for transmission electron microscopy (TEM) is such an example, taking several days. However, for protein-based nanotechnology, high resolution imaging techniques are unique and crucial tools for studying the spatial distribution of these molecules, either alone or as components of biomaterials. In this paper, we tested 2 new short methods of immunolocalization for TEM, and compared them with a standard pr...
Protein-Based Therapeutic Killing for Cancer Therapies Naroa Serna1, Laura Sánchez-García, Ugutz Unzueta, Raquel Díaz, Esther Vázquez, Ramón Mangues, Antonio Villaverde Show more https://doi.org/10.1016/j.tibtech.2017.11.007 Targeting cytotoxic drugs in oncology is essential because side toxicities limit reaching effective local doses. Functionalization of nanoscale drug vehicles has so far achieved a moderate targeting effect. The nanoscale size of drug preparations favors enhanced permeability and retention (EPR) and reduces renal filtration. Proteins are used as inert nanoscale carriers and as functional targeting agents in the form of antibodies or ligands that bind to tumor cell-surface markers. Many protein species exhibit potent cytotoxic ac
https://www.nature.com/articles/s41598-017-17259-4 Disulfide driven folding for a conditionally disordered protein Hugo Fraga, Jordi Pujols, Marcos Gil-Garcia, Alicia Roque, Ganeko Bernardo-Seisdedos, Carlo Santambrogio, Joan-Josep Bech-Serra, Francesc Canals, Pau Bernadó, Rita Grandori, Oscar Millet & Salvador Ventura Abstract Conditionally disordered proteins are either ordered or disordered depending on the environmental context. The substrates of the mitochondrial intermembrane space (IMS) oxidoreductase Mia40 are synthesized on cytosolic ribosomes and diffuse as intrinsically disordered proteins to the IMS, where they fold into their functional conformations; behaving thus as conditionally disordered proteins. It is not clear how the sequences of these polyp
Abstract Oxidatively modified forms of proteins accumulate during aging. Oxidized protein conformers might act as intermediates in the formation of amyloids in age-related disorders. However, it is not known whether this amyloidogenic conversion requires an extensive protein oxidative damage or it can be promoted just by a discrete, localized post-translational modification of certain residues. Here, we demonstrate that the irreversible oxidation of a single free Cyssuffices to severely perturb the folding energy landscape of a stable globular protein, compromise its kinetic stability, and lead to the formation of amyloids under physiological conditions. Experiments and simulations converge to indicate that this specific oxidation-promoted protein aggregation requires only local unfol
Abstract The success of viruses in the delivery of the viral genome to target cells relies on the evolutionary selection of protein-based domains able to hijack the intermolecular interactions through which cells respond to intra- and extracellular stimuli. In an effort to mimic viral infection capabilities during non-viral gene delivery, a modular recombinant protein named T-Rp3 was recently developed, containing a DNA binding domain, a dynein molecular motor interacting domain, and a TAT-derived transduction domain. Here, we analyzed at the microscopic level the mechanisms behind the cell internalization and intracellular trafficking of this highly efficient modular protein vector. We found that the protein has the ability to self-assemble in discrete protein nanoparticles resemblin...
Engineering multifunctional protein nanoparticles by in vitro disassembling and reassembling of heterologous building blocks Ugutz Unzueta1, Naroa Serna2, Laura Sánchez-García3, Mónica Roldan4, Alejandro Sánchez-Chardi5, Ramon Mangues6, Antonio Villaverde Villaverde7 and Esther Vázquez8 http://iopscience.iop.org/article/10.1088/1361-6528/aa963e#top
El 4 d'octubre, entitats de la societat civil catalana, amb la participació de la UAB i la UB, van constituir una Comissió Independent per a la mediació, el diàleg i la conciliació. Ara, totes les universitats catalanes han donat suport a aquesta iniciativa. Totes les universitats catalanes donem suport a la iniciativa de creació d'una comissió independent de mediació, diàleg i conciliació promoguda pel Col·legi de l'Advocacia de Barcelona i altres entitats de la societat civil. Universitat de Barcelona, Universitat Autònoma de Barcelona, Universitat Politècnica de Catalunya, Universitat Pompeu Fabra, Universitat de Lleida, Universitat de Girona, Universitat Rovira i Virgili, Universitat Ramon Llull, Universitat Oberta de Catalunya, Universitat de Vic - Universitat Central de Catalunya
Peptide-Based Nanostructured Materials with Intrinsic Proapoptotic Activities in CXCR4+ Solid Tumors ￼Naroa Serna, ￼María Virtudes Céspedes, ￼Laura Sánchez-García, ￼Ugutz Unzueta, ￼Rita Sala, ￼Alejandro Sánchez-Chardi, ￼Francisco Cortés, ￼Neus Ferrer-Miralles, ￼Ramón Mangues, ￼Esther Vázquez, ￼Antonio Villaverde http://onlinelibrary.wiley.com/doi/10.1002/adfm.201700919/full Abstract Protein materials are gaining interest in nanomedicine because of the unique combination of regulatable function and structure. A main application of protein nanoparticles is as vehicles for cell-targeted drug delivery in the form of nanoconjugates, in which a conventional or innovative drug is associated to a carrier protein. Here, a new nanomedical approach based on self-assembling protein nanoparticl