Nanoscopy for nanomedicine


The main goal of our group is to use Super Resolution Microscopy (nanoscopy) to visualize and track in living cells and tissues self-assembled nanomaterials with therapeutic potential (nanomedicine).

TEM image of novel self-assembled nanofibers synthesized in the group.

The understanding of materials-cell interactions is the key towards the development of novel nanotechnology-based therapies for treatment of cancer and infectious diseases.
Our group aims to use a multidisciplinary approach, at the interface of chemistry, physics and biology, to develop novel nanomaterials for the treatment of cancer and infectious diseases.

We aim at the development of novel nanocarriers for drug delivery based on self-assembly, i.e. able to build themselves. Molecular self-organization is ubiquitous in the biological world and represents for us a source of inspiration for the design of nanostructures with biomedical potential. In particular we focus on the development of self-assembled nanoparticles and nanofibers able to selectively target diseased cells and deliver locally therapeutic moieties such as drugs and genetic material (e.g. DNA, siRNA, mRNA).

Right: Nanoparticles interactions with blood components imaged with conventional optical microscopy (left) and super resolution STORM microscopy (right).

A key point towards the development of novel nanotechnology-based therapies is the understanding of the behavior of nanomaterials in the complex biological environment. Here we use super resolution microscopy to track nanomaterials during their voyage in the biological environment and to visualize the interactions with blood components, immune system and target cells. We make use of a variety of super resolution techniques based on single molecule detection such a stochastic optical reconstruction microscopy (STORM), photoactivated localization microscopy (PALM), point accumulation for imaging in nanoscale topography (PAINT), and single particle tracking (SPT). These methods allow to achieve a resolution down to few nanometers and are therefore ideal to visualize nanosized synthetic objects in the biological environment. Super resolution microscopy provides a molecular picture of structure-activity relations and represent a guide towards the design of innovative materials for nanomedicine.


Lorenzo Albertazzi | Group Leader
Silvia Pujals Riatós | Senior Researcher
Teodora Andrian | PhD Student
Maria Arista Romero | PhD Student
Edgar Fuentes Fuentes | PhD Student
Adrianna Glinkowska Mares | PhD Student
Madhura Vijay Murar | PhD Student
Rodica Alis Olea | PhD Student
Roger Riera Brillas | PhD Student
Marc Pérez Burgos | Masters Student



International grants
NANOSTORM Design of Nanomaterials for Targeted Therapies Guided by Super Resolution Imaging (2018-2023) ERC, European Commission Lorenzo Albertazzi
THERACAT BIO-orthogonal catalysis for cancer therapy (2018-2022) MARIE CURIE, European Commission Lorenzo Albertazzi
National grants
NANOVAX Nanovacunas diseñadas para inmunoterapia antitumoral (2016-2019) Acciones de Programación Conjunta Internacional, MINECO Lorenzo Albertazzi/Josep Samitier
Collaborative Research Projects AOM-BIST BIST Lorenzo Albertazzi
Understanding and measuring mechanical tumor properties to improve cancer  diagnosis, treatment, and survival: Application to liquid biopsies
Obra Social La Caixa Lorenzo Albertazzi
Old projects
Novel approaches for Pandemic Virus Targeting Using Adaptive Polymers (2015-2017) AXA Research Fund Lorenzo Albertazzi
TARGETSTORM Nanomateriales para terapias dirigidas contra el cáncer visualizados con microscopia de súper resolución STORM (2016-2019) Retos investigación: Proyectos I+D, MINECO Silvia Pujals
SGR Grups de recerca consolidats (2017-2019) SGR, AGAUR Silvia Pujals


(See full publication list in ORCID)

Baranov, M. V., Olea, R. A., van den Bogaart, G., (2019). Chasing uptake: Super-resolution microscopy in endocytosis and phagocytosis Trends in Cell Biology 29, (9), 727-739

Since their invention about two decades ago, super-resolution microscopes have become a method of choice in cell biology. Owing to a spatial resolution below 50 nm, smaller than the size of most organelles, and an order of magnitude better than the diffraction limit of conventional light microscopes, superresolution microscopy is a powerful technique for resolving intracellular trafficking. In this review we discuss discoveries in endocytosis and phagocytosis that have been made possible by super-resolution microscopy – from uptake at the plasma membrane, endocytic coat formation, and cytoskeletal rearrangements to endosomal maturation. The detailed visualization of the diverse molecular assemblies that mediate endocytic uptake will provide a better understanding of how cells ingest extracellular material.

Keywords: Endocytosis, Endosomes, Organelles, Super-resolution microscopy, Trafficking

Cozzolino, M., Delcanale, P., Montali, C., Tognolini, M., Giorgio, C., Corrado, M., Cavanna, L., Bianchini, P., Diaspro, A., Abbruzzetti, S., Viappiani, C., (2019). Enhanced photosensitizing properties of protein bound curcumin Life Sciences 233, 116710

Aims: The naturally occurring compound curcumin has been proposed for a number of pharmacological applications. In spite of the promising chemotherapeutic properties of the molecule, the use of curcumin has been largely limited by its chemical instability in water. In this work, we propose the use of water soluble proteins to overcome this issue in perspective applications to photodynamic therapy of tumors. Materials and methods: Curcumin was bound to bovine serum albumin and its photophysical properties was studied as well as its effect on cell viability after light exposure through MTT assay and confocal imaging. Key findings: Bovine serum albumin binds curcumin with moderate affinity and solubilizes the hydrophobic compound preserving its photophysical properties for several hours. Cell viability assays demonstrate that when bound to serum albumin, curcumin is an effective photosensitizer for HeLa cells, with better performance than curcumin alone. Confocal fluorescence imaging reveals that when curcumin is delivered alone, it preferentially associates with mitochondria, whereas curcumin bound to bovine serum albumin is found in additional locations within the cell, a fact that may be related to the higher phototoxicity observed in this case. Significance: The higher bioavailability of the photosensitizing compound curcumin when bound to serum albumin may be exploited to increase the efficiency of the drug in photodynamic therapy of tumors.

Keywords: Cancer, Curcumin, Live cell imaging, Photodynamic therapy

Post, R. A. J., van der Zwaag, D., Bet, G., Wijnands, S. P. W., Albertazzi, L., Meijer, E. W., van der Hofstad, R. W., (2019). A stochastic view on surface inhomogeneity of nanoparticles Nature Communications 10, (1), 1663

The interactions between and with nanostructures can only be fully understood when the functional group distribution on their surfaces can be quantified accurately. Here we apply a combination of direct stochastic optical reconstruction microscopy (dSTORM) imaging and probabilistic modelling to analyse molecular distributions on spherical nanoparticles. The properties of individual fluorophores are assessed and incorporated into a model for the dSTORM imaging process. Using this tailored model, overcounting artefacts are greatly reduced and the locations of dye labels can be accurately estimated, revealing their spatial distribution. We show that standard chemical protocols for dye attachment lead to inhomogeneous functionalization in the case of ubiquitous polystyrene nanoparticles. Moreover, we demonstrate that stochastic fluctuations result in large variability of the local group density between particles. These results cast doubt on the uniform surface coverage commonly assumed in the creation of amorphous functional nanoparticles and expose a striking difference between the average population and individual nanoparticle coverage.

Feiner-Gracia, N., Olea, R. A., Fitzner, R., El Boujnouni, N., Van Asbeck, A. H., Brock, R., Albertazzi, L., (2019). Super-resolution imaging of structure, molecular composition, and stability of single oligonucleotide polyplexes Nano Letters 19, (5), 2784-2792

The successful application of gene therapy relies on the development of safe and efficient delivery vectors. Cationic polymers such as cell-penetrating peptides (CPPs) can condense genetic material into nanoscale particles, called polyplexes, and induce cellular uptake. With respect to this point, several aspects of the nanoscale structure of polyplexes have remained elusive because of the difficulty in visualizing the molecular arrangement of the two components with nanometer resolution. This limitation has hampered the rational design of polyplexes based on direct structural information. Here, we used super-resolution imaging to study the structure and molecular composition of individual CPP-mRNA polyplexes with nanometer accuracy. We use two-color direct stochastic optical reconstruction microscopy (dSTORM) to unveil the impact of peptide stoichiometry on polyplex structure and composition and to assess their destabilization in blood serum. Our method provides information about the size and composition of individual polyplexes, allowing the study of such properties on a single polyplex basis. Furthermore, the differences in stoichiometry readily explain the differences in cellular uptake behavior. Thus, quantitative dSTORM of polyplexes is complementary to the currently used characterization techniques for understanding the determinants of polyplex activity in vitro and inside cells.

Keywords: dSTORM, Gene delivery, Polyplexes, Stability, Super-resolution microscopy

Pujals, S., Feiner-Gracia, N., Delcanale, P., Voets, I., Albertazzi, L., (2019). Super-resolution microscopy as a powerful tool to study complex synthetic materials Nature Reviews Chemistry 3, (2), 68-84

Understanding the relations between the formation, structure, dynamics and functionality of complex synthetic materials is one of the great challenges in chemistry and nanotechnology and represents the foundation for the rational design of novel materials for a variety of applications. Initially conceived to study biology below the diffraction limit, super-resolution microscopy (SRM) is emerging as a powerful tool for studying synthetic materials owing to its nanometric resolution, multicolour ability and minimal invasiveness. In this Review, we provide an overview of the pioneering studies that use SRM to visualize materials, highlighting exciting recent developments such as experiments in operando, wherein materials, such as biomaterials in a biological environment, are imaged in action. Moreover, the potential and the challenges of the different SRM methods for application in nanotechnology and (bio)materials science are discussed, aiming to guide researchers to select the best SRM approach for their specific purpose.

Keywords: Bioinspired materials, Imaging techniques

Pujals, S., Albertazzi, L., (2019). Super-resolution microscopy for nanomedicine research ACS Nano 13, (9), 9707-9712

Super-resolution microscopy, or nanoscopy, revolutionized the field of cell biology, enabling researchers to visualize cellular structures with nanometric resolution, single-molecule sensitivity, and in multiple colors. However, the impact of these techniques goes beyond biology as the fields of nanotechnology and nanomedicine can greatly benefit from them, as well. Nanoscopy can visualize nanostructures in vitro and in cells and can contribute to the characterization of their structures and nano-bio interactions. In this Perspective, we discuss the potential of super-resolution imaging for nanomedicine research, its technical challenges, and the future developments we envision for this technology.

Kolpe, A., Arista-Romero, M., Schepens, B., Pujals, S., Saelens, X., Albertazzi, L., (2019). Super-resolution microscopy reveals significant impact of M2e-specific monoclonal antibodies on influenza A virus filament formation at the host cell surface Scientific Reports 9, (1), 4450

Influenza A virions are highly pleomorphic, exhibiting either spherical or filamentous morphology. The influenza A virus strain A/Udorn/72 (H3N2) produces copious amounts of long filaments on the surface of infected cells where matrix protein 1 (M1) and 2 (M2) play a key role in virus filament formation. Previously, it was shown that an anti-M2 ectodomain (M2e) antibody could inhibit A/Udorn/72 virus filament formation. However, the study of these structures is limited by their small size and complex structure. Here, we show that M2e-specific IgG1 and IgG2a mouse monoclonal antibodies can reduce influenza A/Udorn/72 virus plaque growth and infectivity in vitro. Using Immuno-staining combined with super-resolution microscopy that allows us to study structures beyond the diffraction limit, we report that M2 is localized at the base of viral filaments that emerge from the membrane of infected cells. Filament formation was inhibited by treatment of A/Udorn/72 infected cells with M2e-specific IgG2a and IgG1 monoclonal antibodies and resulted in fragmentation of pre-existing filaments. We conclude that M2e-specific IgGs can reduce filamentous influenza A virus replication in vitro and suggest that in vitro inhibition of A/Udorn/72 virus replication by M2e-specific antibodies correlates with the inhibition of filament formation on the surface of infected cells.

Riera, R., Feiner-Gracia, N., Fornaguera, C., Cascante, A., Borrós, S., Albertazzi, L., (2019). Tracking the DNA complexation state of pBAE polyplexes in cells with super resolution microscopy Nanoscale 11, (38), 17869-17877

The future of gene therapy relies on the development of efficient and safe delivery vectors. Poly(β-amino ester)s are promising cationic polymers capable of condensing oligonucleotides into nanoparticles – polyplexes – and deliver them into the cell nucleus, where the gene material would be expressed. The complexation state during the crossing of biological barriers is crucial: polymers should tightly complex DNA before internalization and then release to allow free DNA to reach the nucleus. However, measuring the complexation state in cells is challenging due to the nanometric size of polyplexes and the difficulties to study the two components (polymer and DNA) independently. Here we propose a method to visualize and quantify the two components of a polyplex inside cells, with nanometre scale resolution, using two-colour direct stochastic reconstruction super-resolution microscopy (dSTORM). With our approach, we tracked the complexation state of pBAE polyplexes from cell binding to DNA release and nuclear entry revealing time evolution and the final fate of DNA and pBAE polymers in mammalian cells.

Uroz, Marina, Garcia-Puig, Anna, Tekeli, Isil, Elosegui-Artola, Alberto, Abenza, Juan F., Marín-Llauradó, Ariadna, Pujals, Silvia, Conte, Vito, Albertazzi, Lorenzo, Roca-Cusachs, Pere, Raya, Ángel, Trepat, Xavier, (2019). Traction forces at the cytokinetic ring regulate cell division and polyploidy in the migrating zebrafish epicardium Nature Materials 18, 1015-1023

Epithelial repair and regeneration are driven by collective cell migration and division. Both cellular functions involve tightly controlled mechanical events, but how physical forces regulate cell division in migrating epithelia is largely unknown. Here we show that cells dividing in the migrating zebrafish epicardium exert large cell–extracellular matrix (ECM) forces during cytokinesis. These forces point towards the division axis and are exerted through focal adhesions that connect the cytokinetic ring to the underlying ECM. When subjected to high loading rates, these cytokinetic focal adhesions prevent closure of the contractile ring, leading to multi-nucleation through cytokinetic failure. By combining a clutch model with experiments on substrates of different rigidity, ECM composition and ligand density, we show that failed cytokinesis is triggered by adhesion reinforcement downstream of increased myosin density. The mechanical interaction between the cytokinetic ring and the ECM thus provides a mechanism for the regulation of cell division and polyploidy that may have implications in regeneration and cancer.

Liu, Yiliu, Pujals, Sílvia, Stals, Patrick J. M., Paulöhrl, Thomas, Presolski, Stanislav I., Meijer, E. W., Albertazzi, Lorenzo, Palmans, Anja R. A., (2018). Catalytically active single-chain polymeric nanoparticles: Exploring their functions in complex biological media Journal of the American Chemical Society 140, (9), 3423-3433

Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media. The ability of SCPNs to act as catalysts in biological media was first assessed by investigating their potential for reactive oxygen species generation. With porphyrins covalently attached to the SCPNs, singlet oxygen was generated upon irradiation with light, inducing spatially controlled cell death. In addition, Cu(I)- and Pd(II)-based SCPNs were prepared and these catalysts were screened in vitro and studied in cellular environments for the carbamate cleavage reaction of rhodamine-based substrates. This is a model reaction for the uncaging of bioactive compounds such as cytotoxic drugs for catalysis-based cancer therapy. We observed that the rate of the deprotection depends on both the organometallic catalysts and the nature of the protective group. The rate reduces from in vitro to the biological environment, indicating a strong influence of biomolecules on catalyst performance. The Cu(I)-based SCPNs in combination with the dimethylpropargyloxycarbonyl protective group showed the best performances both in vitro and in biological environment, making this group promising in biomedical applications.

Patiño, Tania, Feiner-Gracia, Natalia, Arqué, Xavier, Miguel-López, Albert, Jannasch, Anita, Stumpp, Tom, Schäffer, Erik, Albertazzi, Lorenzo, Sánchez, Samuel, (2018). Influence of enzyme quantity and distribution on the self-propulsion of non-Janus urease-powered micromotors Journal of the American Chemical Society 140, (25), 7896-7903

The use of enzyme catalysis to power micro- and nanomachines offers unique features such as biocompatibility, versatility, and fuel bioavailability. Yet, the key parameters underlying the motion behavior of enzyme-powered motors are not completely understood. Here, we investigate the role of enzyme distribution and quantity on the generation of active motion. Two different micromotor architectures based on either polystyrene (PS) or polystyrene coated with a rough silicon dioxide shell (PS@SiO2) were explored. A directional propulsion with higher speed was observed for PS@SiO2 motors when compared to their PS counterparts. We made use of stochastically optical reconstruction microscopy (STORM) to precisely detect single urease molecules conjugated to the micromotors surface with a high spatial resolution. An asymmetric distribution of enzymes around the micromotor surface was observed for both PS and PS@SiO2 architectures, indicating that the enzyme distribution was not the only parameter affecting the motion behavior. We quantified the number of enzymes present on the micromotor surface and observed a 10-fold increase in the number of urease molecules for PS@SiO2 motors compared to PS-based micromotors. To further investigate the number of enzymes required to generate a self-propulsion, PS@SiO2 particles were functionalized with varying amounts of urease molecules and the resulting speed and propulsive force were measured by optical tracking and optical tweezers, respectively. Surprisingly, both speed and force depended in a nonlinear fashion on the enzyme coverage. To break symmetry for active propulsion, we found that a certain threshold number of enzymes molecules per micromotor was necessary, indicating that activity may be due to a critical phenomenon. Taken together, these results provide new insights into the design features of micro/nanomotors to ensure an efficient development.

Delcanale, Pietro, Miret-Ontiveros, Bernat, Arista-Romero, Maria, Pujals, Silvia, Albertazzi, Lorenzo, (2018). Nanoscale mapping functional sites on nanoparticles by Points Accumulation for Imaging in Nanoscale Topography (PAINT) ACS Nano 12, (8), 7629-7637

The ability of nanoparticles to selectively recognize a molecular target constitutes the key toward nanomedicine applications such as drug delivery and diagnostics. The activity of such devices is mediated by the presence of multiple copies of functional molecules on the nanostructure surface. Therefore, understanding the number and the distribution of nanoparticle functional groups is of utmost importance for the rational design of effective materials. Analytical methods are available, but to obtain quantitative information at the level of single particles and single functional sites, i.e., going beyond the ensemble, remains highly challenging. Here we introduce the use of an optical nanoscopy technique, DNA points accumulation for imaging in nanoscale topography (DNA-PAINT), to address this issue. Combining subdiffraction spatial resolution with molecular selectivity and sensitivity, DNA-PAINT provides both geometrical and functional information at the level of a single nanostructure. We show how DNA-PAINT can be used to image and quantify relevant functional proteins such as antibodies and streptavidin on nanoparticles and microparticles with nanometric accuracy in 3D and multiple colors. The generality and the applicability of our method without the need for fluorescent labeling hold great promise for the robust quantitative nanocharacterization of functional nanomaterials.

Ardizzone, Antonio, Kurhuzenkau, Siarhei, Illa-Tuset, Sílvia, Faraudo, Jordi, Bondar, Mykhailo, Hagan, David, Van Stryland, Eric W., Painelli, Anna, Sissa, Cristina, Feiner, Natalia, Albertazzi, Lorenzo, Veciana, Jaume, Ventosa, Nora, (2018). Nanostructuring lipophilic dyes in water using stable vesicles, quatsomes, as scaffolds and their use as probes for bioimaging Small 14, (16), 1703851

Abstract A new kind of fluorescent organic nanoparticles (FONs) is obtained using quatsomes (QSs), a family of nanovesicles proposed as scaffolds for the nanostructuration of commercial lipophilic carbocyanines (1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI), 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indodicarbocyanine perchlorate (DiD), and 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indotricarbocyanine iodide (DiR)) in aqueous media. The obtained FONs, prepared by a CO2-based technology, show excellent colloidal- and photostability, outperforming other nanoformulations of the dyes, and improve the optical properties of the fluorophores in water. Molecular dynamics simulations provide an atomistic picture of the disposition of the dyes within the membrane. The potential of QSs for biological imaging is demonstrated by performing superresolution microscopy of the DiI-loaded vesicles in vitro and in cells. Therefore, fluorescent QSs constitute an appealing nanomaterial for bioimaging applications.

Casellas, Nicolas M., Pujals, Sílvia, Bochicchio, Davide, Pavan, Giovanni M., Torres, Tomás, Albertazzi, Lorenzo, García-Iglesias, Miguel, (2018). From isodesmic to highly cooperative: Reverting the supramolecular polymerization mechanism in water by fine monomer design Chemical Communications 54, (33), 4112-4115

Two structurally-similar discotic molecules able to self-assemble in water, forming supramolecular fibers, are reported. While both self-assembled polymers are indistinguishable from a morphological point-of-view, a dramatic change in their polymerization mechanism is observed (i.e., one self-assemble via an isodesmic mechanism, while the other shows one of the highest cooperativity values).

Krivitsky, Adva, Polyak, Dina, Scomparin, Anna, Eliyahu, Shay, Ofek, Paula, Tiram, Galia, Kalinski, Hagar, Avkin-Nachum, Sharon, Feiner Gracia, N., Albertazzi, Lorenzo, Satchi-Fainaro, Ronit, (2018). Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors Nanomedicine: Nanotechnology, Biology, and Medicine 14, (2), 303-315

RNAi therapeutics carried a great promise to the area of personalized medicine: the ability to target “undruggable” oncogenic pathways. Nevertheless, their efficient tumor targeting via systemic administration had not been resolved yet. Amphiphilic alkylated poly(α)glutamate amine (APA) can serve as a cationic carrier to the negatively-charged oligonucleotides. APA polymers complexed with siRNA to form round-shaped, homogenous and reproducible nano-sized polyplexes bearing ~50 nm size and slightly negative charge. In addition, APA:siRNA polyplexes were shown to be potent gene regulators in vitro. In light of these preferred physico-chemical characteristics, their performance as systemically-administered siRNA nanocarriers was investigated. Intravenously-injected APA:siRNA polyplexes accumulated selectively in tumors and did not accumulate in the lungs, heart, liver or spleen. Nevertheless, the polyplexes failed to induce specific mRNA degradation, hence neither reduction in tumor volume nor prolonged mice survival was seen.

van Elsland, Daphne M., Pujals, Sílvia, Bakkum, Thomas, Bos, Erik, Oikonomeas-Koppasis, Nikolaos, Berlin, Ilana, Neefjes, Jacques, Meijer, Annemarie H., Koster, Abraham J., Albertazzi, Lorenzo, van Kasteren, Sander I., (2018). Ultrastructural imaging of salmonella-host interactions using super-resolution correlative light-electron microscopy of bioorthogonal pathogens ChemBioChem 19, (16), 1766-1770

The imaging of intracellular pathogens inside host cells is complicated by the low resolution and sensitivity of fluorescence microscopy and by the lack of ultrastructural information to visualize the pathogens. Herein, we present a new method to visualize these pathogens during infection that circumvents these problems: by using a metabolic hijacking approach to bioorthogonally label the intracellular pathogen Salmonella Typhimurium and by using these bioorthogonal groups to introduce fluorophores compatible with stochastic optical reconstruction microscopy (STORM) and placing this in a correlative light electron microscopy (CLEM) workflow, the pathogen can be imaged within its host cell context Typhimurium with a resolution of 20 nm. This STORM-CLEM approach thus presents a new approach to understand these pathogens during infection.

Oria, Roger, Wiegand, Tina, Escribano, Jorge, Elosegui-Artola, Alberto, Uriarte, Juan Jose, Moreno-Pulido, Cristian, Platzman, Ilia, Delcanale, Pietro, Albertazzi, Lorenzo, Navajas, Daniel, Trepat, Xavier, García-Aznar, José Manuel, Cavalcanti-Adam, Elisabetta Ada, Roca-Cusachs, Pere, (2017). Force loading explains spatial sensing of ligands by cells Nature 552, 219-224

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts1,2. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin–ligand bonds are separated by more than a few tens of nanometres3,4,5,6. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly3,7,8,9. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model10,11, in which individual integrin–ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds support our model. Our results provide a general framework for how cells sense spatial and physical information at the nanoscale, precisely tuning the range of conditions at which they form adhesions and activate transcriptional regulation.

Duro-Castano, Aroa, Nebot, Vicent J., Niño-Pariente, Amaya, Armiñán, Ana, Arroyo-Crespo, Juan J., Paul, Alison, Feiner-Gracia, Natalia, Albertazzi, Lorenzo, Vicent, María J., (2017). Capturing “extraordinary” soft-assembled charge-like polypeptides as a strategy for nanocarrier design Advanced Materials , 29, (39), 1702888

The rational design of nanomedicines is a challenging task given the complex architectures required for the construction of nanosized carriers with embedded therapeutic properties and the complex interface of these materials with the biological environment. Herein, an unexpected charge-like attraction mechanism of self-assembly for star-shaped polyglutamates in nonsalty aqueous solutions is identified, which matches the ubiquitous “ordinary–extraordinary” phenomenon previously described by physicists. For the first time, a bottom-up methodology for the stabilization of these nanosized soft-assembled star-shaped polyglutamates is also described, enabling the translation of theoretical research into nanomaterials with applicability within the drug-delivery field. Covalent capture of these labile assemblies provides access to unprecedented architectures to be used as nanocarriers. The enhanced in vitro and in vivo properties of these novel nanoconstructs as drug-delivery systems highlight the potential of this approach for tumor-localized as well as lymphotropic delivery.

Keywords: Charge-like, Drug delivery, Polymer therapeutics, Polypeptides, Self-assembly

Labernadie, A., Kato, T., Brugués, A., Serra-Picamal, X., Derzsi, S., Arwert, E., Weston, A., González-Tarragó, V., Elosegui-Artola, A., Albertazzi, L., Alcaraz, J., Roca-Cusachs, P., Sahai, E., Trepat, X., (2017). A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion Nature Cell Biology 19, (3), 224-237

Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion. N-cadherin also mediates repolarization of the CAFs away from the cancer cells. In parallel, nectins and afadin are recruited to the cancer cell/CAF interface and CAF repolarization is afadin dependent. Heterotypic junctions between CAFs and cancer cells are observed in patient-derived material. Together, our findings show that a mechanically active heterophilic adhesion between CAFs and cancer cells enables cooperative tumour invasion.

Feiner-Gracia, Natalia, Buzhor, Marina, Fuentes, Edgar, Pujals, S., Amir, Roey J., Albertazzi, Lorenzo, (2017). Micellar stability in biological media dictates internalization in living cells Journal of the American Chemical Society 139, (46), 16677-16687

The dynamic nature of polymeric assemblies makes their stability in biological media a crucial parameter for their potential use as drug delivery systems in vivo. Therefore, it is essential to study and understand the behavior of self-assembled nanocarriers under conditions that will be encountered in vivo such as extreme dilutions and interactions with blood proteins and cells. Herein, using a combination of fluorescence spectroscopy and microscopy, we studied four amphiphilic PEG–dendron hybrids and their self-assembled micelles in order to determine their structure–stability relations. The high molecular precision of the dendritic block enabled us to systematically tune the hydrophobicity and stability of the assembled micelles. Using micelles that change their fluorescent properties upon disassembly, we observed that serum proteins bind to and interact with the polymeric amphiphiles in both their assembled and monomeric states. These interactions strongly affected the stability and enzymatic degradation of the micelles. Finally, using spectrally resolved confocal imaging, we determined the relations between the stability of the polymeric assemblies in biological media and their cell entry. Our results highlight the important interplay between molecular structure, micellar stability, and cell internalization pathways, pinpointing the high sensitivity of stability–activity relations to minor structural changes and the crucial role that these relations play in designing effective polymeric nanostructures for biomedical applications.

Feiner-Gracia, Natalia, Beck, Michaela, Pujals, Sílvia, Tosi, Sébastien, Mandal, Tamoghna, Buske, Christian, Linden, Mika, Albertazzi, Lorenzo, (2017). Super-resolution microscopy unveils dynamic heterogeneities in nanoparticle protein corona Small 13, (41), 1701631

The adsorption of serum proteins, leading to the formation of a biomolecular corona, is a key determinant of the biological identity of nanoparticles in vivo. Therefore, gaining knowledge on the formation, composition, and temporal evolution of the corona is of utmost importance for the development of nanoparticle-based therapies. Here, it is shown that the use of super-resolution optical microscopy enables the imaging of the protein corona on mesoporous silica nanoparticles with single protein sensitivity. Particle-by-particle quantification reveals a significant heterogeneity in protein absorption under native conditions. Moreover, the diversity of the corona evolves over time depending on the surface chemistry and degradability of the particles. This paper investigates the consequences of protein adsorption for specific cell targeting by antibody-functionalized nanoparticles providing a detailed understanding of corona-activity relations. The methodology is widely applicable to a variety of nanostructures and complements the existing ensemble approaches for protein corona study.

Keywords: Heterogeneity, Mesoporous silica nanoparticles, Protein corona, Super-resolution imaging, Targeting

Van Onzen, A. H. A. M., Albertazzi, L., Schenning, A. P. H. J., Milroy, L. G., Brunsveld, L., (2017). Hydrophobicity determines the fate of self-assembled fluorescent nanoparticles in cells Chemical Communications 53, (10), 1626-1629

The fate of small molecule nanoparticles (SMNPs) composed of self-assembling intrinsically fluorescent π-conjugated oligomers was studied in cells as a function of side-chain hydrophobicity. While the hydrophobic SMNPs remained intact upon cellular uptake, the more hydrophilic SMNPs disassembled and dispersed throughout the cytosol.

Pujals, S., Tao, K., Terradellas, A., Gazit, E., Albertazzi, L., (2017). Studying structure and dynamics of self-Assembled peptide nanostructures using fluorescence and super resolution microscopy Chemical Communications 53, (53), 7294-7297

Understanding the formation and properties of self-Assembled peptide nanostructures is the basis for the design of new architectures for various applications. Here we show the potential of fluorescence and super resolution imaging to unveil the structural and dynamic features of peptide nanofibers with high spatiotemporal resolution.

Caballero, David, Blackburn, Sophie M., de Pablo, Mar, Samitier, Josep, Albertazzi, Lorenzo, (2017). Tumour-vessel-on-a-chip models for drug delivery Lab on a Chip 17, 3760-3771

Nanocarriers for drug delivery have great potential to revolutionize cancer treatment, due to their enhanced selectivity and efficacy. Despite this great promise, researchers have had limited success in the clinical translation of this approach. One of the main causes of these difficulties is that standard in vitro models, typically used to understand nanocarriers' behaviour and screen their efficiency, do not provide the complexity typically encountered in living systems. In contrast, in vivo models, despite being highly physiological, display serious bottlenecks which threaten the relevancy of the obtained data. Microfluidics and nanofabrication can dramatically contribute to solving this issue, providing 3D high-throughput models with improved resemblance to in vivo systems. In particular, microfluidic models of tumour blood vessels can be used to better elucidate how new nanocarriers behave in the microcirculation of healthy and cancerous tissues. Several key steps of the drug delivery process such as extravasation, immune response and endothelial targeting happen under flow in capillaries and can be accurately modelled using microfluidics. In this review, we will present how tumour-vessel-on-a-chip systems can be used to investigate targeted drug delivery and which key factors need to be considered for the rational design of these materials. Future applications of this approach and its role in driving forward the next generation of targeted drug delivery methods will be discussed.

Bakker, Maarten H., Lee, Cameron C., Meijer, E. W., Dankers, Patricia Y. W., Albertazzi, Lorenzo, (2016). Multicomponent supramolecular polymers as a modular platform for intracellular delivery ACS Nano 10, (2), 1845-1852

Supramolecular polymers are an emerging family of nanosized structures with potential use in materials chemistry and medicine. Surprisingly, application of supramolecular polymers in the field of drug delivery has received only limited attention. Here, we explore the potential of PEGylated 1,3,5-benzenetricarboxamide (BTA) supramolecular polymers for intracellular delivery. Exploiting the unique modular approach of supramolecular chemistry, we can coassemble neutral and cationic BTAs and control the overall properties of the polymer by simple monomer mixing. Moreover, this platform offers a versatile approach toward functionalization. The core can be efficiently loaded with a hydrophobic guest molecule, while the exterior can be electrostatically complexed with siRNA. It is demonstrated that both compounds can be delivered in living cells, and that they can be combined to enable a dual delivery strategy. These results show the advantages of employing a modular system and pave the way for application of supramolecular polymers in intracellular delivery.

Beun, L. H., Albertazzi, L., Van Der Zwaag, D., De Vries, R., Cohen Stuart, M. A., (2016). Unidirectional living growth of self-assembled protein nanofibrils revealed by super-resolution microscopy ACS Nano 10, (5), 4973-4980

Protein-based nanofibrils are emerging as a promising class of materials that provide unique properties for applications such as biomedical and food engineering. Here, we use atomic force microscopy and stochastic optical reconstruction microscopy imaging to elucidate the growth dynamics, exchange kinetics, and polymerization mechanism for fibrils composed of a de novo designed recombinant triblock protein polymer. This macromolecule features a silk-inspired self-assembling central block composed of GAGAGAGH repeats, which are known to fold into a β roll with turns at each histidine and, once folded, to stack, forming a long, ribbon-like structure. We find several properties that allow the growth of patterned protein nanofibrils: the self-assembly takes place on only one side of the growing fibrils by the essentially irreversible addition of protein polymer subunits, and these fibril ends remain reactive indefinitely in the absence of monomer ("living ends"). Exploiting these characteristics, we can grow stable diblock protein nanofibrils by the sequential addition of differently labeled proteins. We establish control over the block length ratio by simply varying monomer feed conditions. Our results demonstrate the use of engineered protein polymers in creating precisely patterned protein nanofibrils and open perspectives for the hierarchical self-assembly of functional biomaterials.

Keywords: Nanofibrils, Protein polymers, Self-assembly, STORM microscopy

Garzoni, M., Baker, M. B., Leenders, C. M. A., Voets, I. K., Albertazzi, L., Palmans, A. R. A., Meijer, E. W., Pavan, G. M., (2016). Effect of H-bonding on order amplification in the growth of a supramolecular polymer in water Journal of the American Chemical Society 138, (42), 13985-13995

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins has resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA)-based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the basis of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous evidence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the level of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship directly linking the structure of the monomer to the structure and properties of the supramolecular polymer.

Aloi, Antonio, Vargas Jentzsch, Andreas, Vilanova, Neus, Albertazzi, Lorenzo, Meijer, E. W., Voets, Ilja K., (2016). Imaging nanostructures by single-molecule localization microscopy in organic solvents Journal of the American Chemical Society 138, (9), 2953-2956

The introduction of super-resolution fluorescence microscopy (SRM) opened an unprecedented vista into nanoscopic length scales, unveiling a new degree of complexity in biological systems in aqueous environments. Regrettably, supramolecular chemistry and material science benefited far less from these recent developments. Here we expand the scope of SRM to photoactivated localization microscopy (PALM) imaging of synthetic nanostructures that are highly dynamic in organic solvents. Furthermore, we characterize the photophysical properties of commonly used photoactivatable dyes in a wide range of solvents, which is made possible by the addition of a tiny amount of an alcohol. As proof-of-principle, we use PALM to image silica beads with radii close to Abbe’s diffraction limit. Individual nanoparticles are readily identified and reliably sized in multicolor mixtures of large and small beads. We further use SRM to visualize nm-thin yet μm-long dynamic, supramolecular polymers, which are among the most challenging molecular systems to image.

da Silva, Ricardo M. P., van der Zwaag, Daan, Albertazzi, Lorenzo, Lee, Sungsoo S., Meijer, E. W., Stupp, Samuel I., (2016). Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres Nature Communications 7, 11561

The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of [beta]-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function.

De Koker, Stefaan, Cui, Jiwei, Vanparijs, Nane, Albertazzi, Lorenzo, Grooten, Johan, Caruso, Frank, De Geest, Bruno G., (2016). Engineering polymer hydrogel nanoparticles for lymph node-targeted delivery Angewandte Chemie - International Edition , 55, (4), 1334-1339

The induction of antigen-specific adaptive immunity exclusively occurs in lymphoid organs. As a consequence, the efficacy by which vaccines reach these tissues strongly affects the efficacy of the vaccine. Here, we report the design of polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (ca. 200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association in vitro, but dramatically improves their lymphatic drainage in vivo. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Keywords: Dendritic cells, Disulfides, Hydrogels, Nanoparticles, Vaccines

Li, Hui, Fierens, Kaat, Zhang, Zhiyue, Vanparijs, Nane, Schuijs, Martijn J., Van Steendam, Katleen, Feiner Gracia, Natàlia, De Rycke, Riet, De Beer, Thomas, De Beuckelaer, Ans, De Koker, Stefaan, Deforce, Dieter, Albertazzi, Lorenzo, Grooten, Johan, Lambrecht, Bart N., De Geest, Bruno G., (2016). Spontaneous protein adsorption on graphene oxide nanosheets allowing efficient intracellular vaccine protein delivery ACS Applied Materials & Interfaces 8, (2), 1147-1155

Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer. Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer.

van der Zwaag, Daan, Vanparijs, Nane, Wijnands, Sjors, De Rycke, Riet, De Geest, Bruno G., Albertazzi, Lorenzo, (2016). Super resolution imaging of nanoparticles cellular uptake and trafficking ACS Applied Materials & Interfaces 8, (10), 6391-6399

Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects. Here we introduce a combination of super-resolution microscopy and single-molecule data analysis to unveil the behavior of nanoparticles during their entry into mammalian cells. Two-color Stochastic Optical Reconstruction Microscopy (STORM) addresses the size and positioning of nanoparticles inside cells and probes their interaction with the cellular machineries at nanoscale resolution. Moreover, we develop image analysis tools to extract quantitative information about internalized particles from STORM images. To demonstrate the potential of our methodology, we extract previously inaccessible information by the direct visualization of the nanoparticle uptake mechanism and the intracellular tracking of nanoparticulate model antigens by dendritic cells. Finally, a direct comparison between STORM, confocal microscopy, and electron microscopy is presented, showing that STORM can provide novel and complementary information on nanoparticle cellular uptake. Understanding the interaction between synthetic nanostructures and living cells is of crucial importance for the development of nanotechnology-based intracellular delivery systems. Fluorescence microscopy is one of the most widespread tools owing to its ability to image multiple colors in native conditions. However, due to the limited resolution, it is unsuitable to address individual diffraction-limited objects. Here we introduce a combination of super-resolution microscopy and single-molecule data analysis to unveil the behavior of nanoparticles during their entry into mammalian cells. Two-color Stochastic Optical Reconstruction Microscopy (STORM) addresses the size and positioning of nanoparticles inside cells and probes their interaction with the cellular machineries at nanoscale resolution. Moreover, we develop image analysis tools to extract quantitative information about internalized particles from STORM images. To demonstrate the potential of our methodology, we extract previously inaccessible information by the direct visualization of the nanoparticle uptake mechanism and the intracellular tracking of nanoparticulate model antigens by dendritic cells. Finally, a direct comparison between STORM, confocal microscopy, and electron microscopy is presented, showing that STORM can provide novel and complementary information on nanoparticle cellular uptake.

Beuwer, Michael A., Knopper, M. F., Albertazzi, Lorenzo, van der Zwaag, Daan, Ellenbroek, Wouter G., Meijer, E. W., Prins, Menno W. J., Zijlstra, Peter, (2016). Mechanical properties of single supramolecular polymers from correlative AFM and fluorescence microscopy Polymer Chemistry 7, (47), 7260-7268

We characterize the structure and mechanical properties of 1,3,5-benzenetricarboxamide (BTA) supramolecular polymers using correlative AFM and fluorescence imaging. AFM allows for nanoscale structural investigation but we found that statistical analysis is difficult because these structures are easily disrupted by the AFM tip. We therefore correlate AFM and fluorescence microscopy to couple nanoscale morphological information to far-field optical images. A fraction of the immobilized polymers are in a clustered or entangled state, which we identify based on diffraction limited fluorescence images. We find that clustered and entangled polymers exhibit a significantly longer persistence length that is broader distributed than single unentangled polymers. By comparison with numerical simulations we find significant heterogeneity in the persistence length of single unentangled polymers, which we attribute to polymer-substrate interactions and the presence of structural diversity within the polymer.


  • Nikon NSTORM Super Resolution Microscope
  • Super Resolution microscopy
  • Single particles tracking
  • TIRF fluorescence imaging


  • Roey Amir
    Tel Aviv University, Israel
  • Mika Linden
    Ulm University, Germany
  • Ilja Voets
    Eindhoven University of Technology, The Netherlands
  • Giovanni Pavan
    SUPSI, Switzerland
  • Bruno De Geest
    University of Ghent, Belgium
  • Salvador Borros
    IQS, Barcelona


Nous blocs químics de “lego” per a solucions de salut

Investigadors de l’IBEC desenvolupen noves molècules de resposta múltiple capaces d’autoassemblar-se en l’aigua formant estructures fibroses. Les anomenades molècules discòtiques mostren sensibilitat a la temperatura, la llum, el pH i la força iònica i poden mostrar un gran potencial per a aplicacions mèdiques com sistemes d’administració de medicaments, diagnòstic o enginyeria de teixits.

Edgar Fuentes és un estudiant de doctorat al grup de Nanoscopia per a la Nanomedicina dirigit per Lorenzo Albertazzi a l’Institut de Bioenginyeria de Catalunya (IBEC). Dins d’aquest grup, Edgar i els seus col·legues se centren en la síntesi de nous materials supramoleculars intel·ligents per a l’administració de medicaments.

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El president del Consell Europeu d’Investigació visita l’IBEC

El president del Consell Europeu d’Investigació (ERC), Jean-Pierre Bourguignon, va visitar el passat 15 de maig l’Institut de Bioenginyeria de Catalunya (IBEC).

L’esdeveniment va ser inaugurat pel director de l’IBEC, Josep Samitier, qui va presentar una visió general de la investigació d’avantguarda portada que s realitza a l’Institut als camps de la bioenginyeria i la nanomedicina.

Posteriorment, els investigadors amb concessió de fons ERC que treballem a l’IBEC van explicar com aquestes subvencions han les seves carreres professionals, i establir un diàleg amb el president de l’ERC sobre el passat, el present i el futur del Consell Europeu d’investigació.

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