Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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Ion-dependent nanomechanics and molecular organization in quatsome membranes
(Elsevier B.V., 2027-01-01) Pujol Solé, Nuria; Domingo Tafalla, Beatriu; Ratera, Imma; Grisanti, Luca; Carlá, Francesco; Ventosa, Nora; Pedersen, Jakob Skou; Kober, Marina; Reigada Sanz, Ramon; Giannotti, Marina Inés
Quatsomes (QS) are highly stable unilamellar nanovesicles formed by the self-assembly of quaternary ammonium surfactants and sterols. Despite their growing potential as nanocarriers, the molecular determinants of QS membrane structure and mechanics remain poorly understood, limiting the rational design of optimized formulations. Here, we investigate the effect of surfactant chain length, counterion identity, and solution ionic content on the structural and nanomechanical properties of cholesterol-based QS membranes assembled from alkyltrimethylammonium (CnTA+) salts. Supported bilayers and multilamellar membrane stacks were characterized under varying ionic conditions using atomic force microscopy (AFM), X-ray reflectivity, and molecular dynamics simulations. While surfactant chain length had only minor effects on membrane stiffness and negligible influence on fluidity, counterion identity emerged as the dominant factor governing membrane behavior. Smaller chaotropic tendence, as provided by Cl- compared to Br-, promoted tighter molecular packing, resulting in more compact, stiffer membranes with reduced fluidity and greaterresistance to AFM tip penetration. These findings highlight the critical role of ionic composition in regulating QSmembrane organization and mechanics, providing a framework for the rational design of QS-basednanomaterials.
A simple diagnostic platform reveals shear stress as critical in biofilm development
(Elsevier B.V., 2026-12-01) Blanco-Cabra, Núria; Huguet Suarez, Jose; Samitier i Martí, Josep; Rodriguez Trujillo, Romen; Torrents Serra, Eduard
Biofilms are complex microbial communities that exhibit increased tolerance to antibiotics, posing significant challenges in treating chronic infections and highlighting the need for more accurate and personalized diagnostic approaches, as well as simple and accessible platforms for growing biofilms under controlled flow conditions that better mimic in vivo environments. The XpertBiofilm is a novel platform designed to reproduce dynamic flow conditions by applying controlled shear stress, enabling a more realistic simulation of biofilm formation while allowing straightforward downstream analysis. Using this platform, we demonstrated a direct relationship between shear stress and biofilm biomass formation in Pseudomonas aeruginosa. Moreover, the XpertBiofilm was successfully validated for diagnostic applications using both clinical P. aeruginosa strains and direct sputum samples from cystic fibrosis patients, accurately reflecting their known susceptibility profiles and supporting the platform’s potential to enable better patient treatment selection. Overall, the XpertBiofilm provides a reliable, user-friendly, and physiologically relevant platform for studying biofilms and evaluating therapeutic strategies, offering strong potential for both basic research and personalized clinical diagnostics.
Dynamics of supracellular keratin bundling and nuclear uncaging in stretched epithelia
(Nature Publishing Group, 2026-09-01) Golde, Tom; Pensalfini, Marco; Chahare, Nimesh; Roca-Cusachs Soulere, Pere; Wiche, Gerhard; Charras, Guillaume; Arroyo, Marino; Trepat Guixer, Xavier
There is broad consensus that intermediate filaments, such as keratin, play a key role in protecting cells and tissues from large deformations. However, little is known about how they fulfil this function. Here we show that epithelial cells slowly adapt to stretching through a coupling of a star-bundling transition of keratin filaments with the escape of the nucleus from its keratin cage. The bundling transition begins with a depletion of keratin filaments at tricellular junctions followed by a progressive accumulation in thick bundles that bisect cell-cell junctions. Bundling is a cooperative process that initiates in a few scattered cells and propagates to their neighbours, leading to the growth of multicellular clusters that contain a percolated network of thick keratin bundles. Bundling dynamics are slow and strongly influenced by the interaction between actin and keratin. Informed by a computational model, we provide evidence that keratin bundling generates a compressive stress on the nucleus, which is relaxed by nuclear escape from the keratin cage. The topological transitions identified here provide epithelia with a multiscale mechanism to adapt to sustained stretching.
Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton
(Nature Publishing Group, 2026-07-01) Beedle, Amy E. M.; Sharma, Vivek; Oliver de la Cruz, Jorge; Jaganathan, Anuja; Albajar Sigalés, Aina; Max Yavitt, F.; Bera, Kaustav; Andreu Arzuaga, Ion; Granero Moya, Ignasi; Zalvidea, Dobryna; Kechagia, Zanetta; Wiche, Gerhard; Trepat Guixer, Xavier; Ivaska, Johanna; Anseth, Kristi S.; Shenoy, Vivek B.; Roca-Cusachs Soulere, Pere
The cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate the transmission, timing and duration of these signals. Although such timescale regulation is well described for chemical signals, whether and how it applies to mechanical signals reaching the nucleus is still not fully understood. Here we demonstrate that the formation of fibrillar adhesions locks the nucleus in a mechanically deformed conformation, setting the mechano-response timescale to that of fibrillar adhesion remodelling (~1 h). This process encompasses both mechanical deformation and associated mechanotransduction (such as via YAP), in response to both increased and decreased mechanical stimulation. The underlying mechanism is the anchoring of the vimentin cytoskeleton to fibrillar adhesions and the extracellular matrix through plectin 1f, which maintains nuclear deformation. Our results reveal a mechanism to regulate the timescale of mechanical adaptation, effectively setting a low-pass filter to mechanotransduction.
Silicon-based nanopillars: a novel platform for tissue applications
(Royal Society of Chemistry, 2025-12-21) Piergallini, Cristiano ; Díaz Valdivia, Natalia; Deyà, Alba; Fernández Nogueira, Patricia; Singh, Rahul ; Bertelsen, Christian Vinther; Svendsen, Winnie Edith; Corominas, Montserrat (Corominas Guiu); Gombau, Lourdes ; Sanz Fraile, Héctor; Reguart, Noemí; Romano Rodríguez, Albert; Serras Rigalt, Florenci; Luna, Noemí de ; Alcaraz Casademunt, Jordi; Ollé Monge, Marta
Nanostructured surfaces are increasingly used for cell applications due to their enhanced interactions with numerous cell types; yet, their effects on tissues remain unexplored. To address this limitation, we designed vertical silicon nanopillar (Si-NP) arrays with high density, high aspect ratio and submicrometer diameter, as an optimized geometry based on previous cell-nanostructure studies. Using state-of-the-art in vitro and ex vivo assays, we examined adhesion and biocompatibility of biological samples of different origin and level of complexity -human epithelial-like cell lines, Drosophila imaginal discs and patient-derived lung cancer biopsies-laid on Si-NP arrays or unpatterned flat Si surfaces. Our results demonstrated that Si-NP arrays significantly improved cell and tissue adhesion while preventing oxidative damage and early apoptosis. Consistently, focused ion beam-scanning electron microscopy imaging of cells and tissues showed extended horizontal protrusions and limited vertical wrapping around Si-NP, revealing enhanced cell-NP interactions without cell/tissue penetration. In contrast, flat Si surfaces showed poor adhesion, increased apoptosis, and failed to support tumor biopsy attachment. Interaction with Si-NP arrays upregulated reactive oxygen species (ROS), yet mitochondria-associated ROS remained unchanged, and consequently apoptosis was not induced, indicating that the increased ROS arose from non-mitochondrial compartments and did not compromise viability. Notably, Si-NP arrays matched or outperformed biological responses on tissue culture plastic and Transwell-based assays, which are common in vitro and ex vivo substrates, respectively. These findings provide the first demonstration of the biological suitability of Si-NP arrays for tissue applications in research and clinical translation.
Metabolic Screening of Gut Microbiota by Fourier-Transform Infrared Spectroscopy
(American Chemical Society, 2026-06-12) Sayol Altarriba, Anna; Aira Gómez, Andrea; Martín-López, Eva; Villasante, Anna; Albarracín, Rosa; Faneca, Joana; Pitart, Cristina; Roca Subirà, Ignasi; Casals Mercadal, Gregori; Marco Colás, Santiago; Villanueva Cañas, José Luis; Casals Pascual, Climent
Short-chain fatty acids (SCFAs) are bacterial metabolites with crucial roles in host homeostasis and immune system modulation. Given their benefits, they have been proposed as markers of healthy microbiota. However, accurate SCFA quantification typically requires gas chromatography coupled with mass spectrometry (GC-MS), which is time-consuming, expensive, and requires specialized personnel and equipment, limiting its routine use for stool quality assessment in clinical contexts. In this initial feasibility study, we explored the use of Fourier transform infrared (FT-IR) spectroscopy as a rapid metabolic screening approach for stool samples. Analysis of SCFA-associated spectral windows enhanced discrimination between healthy and dysbiotic stool samples with <em>Clostridioides difficile</em> infection using principal component analysis. FT-IR is not intended to replace GC-MS for precise SCFA quantification but rather to provide a rapid screening of metabolically relevant differences. Although additional validation is still needed, the present study provides a robust proof-of-concept demonstrating the feasibility of applying FT-IR spectroscopy to clinical stool samples. Combined with the widespread availability of this technology in most hospitals, these advantages highlight its potential for future development as a tool for routine screening in clinical laboratories.
Late-stage modification of the alkaloid toxin veratridine to photocontrol excitable tissues
(Elsevier Masson, 2026-05-25) Camerin, Luisa; Malieieva, Galyna; Ramírez Abreu, Ailín; Cilleros Mañé, Víctor; Miftari, Drilon; Batlle, Montserrat; Matera, Carlo; Guasch, Eduard; Gorostiza Langa, Pau
Natural products and their structural derivatives have long played a crucial role in the discovery of new medical treatments and pharmacotherapies. However, certain natural compounds, such as toxins, are classified as hazardous substances that pose risk to human health. It is desirable to modulate the activity of toxins to minimize their harmful effects and unleash their potential as selective and bioavailable drugs. Yet, the functionalization of natural products remains a challenge due to their structural complexity. Here, we present two methods for late-stage C-H nitration and subsequent derivatization of the alkaloid steroidal neurotoxin veratridine, a sodium channel opener, by introducing an azobenzene photoswitch in its structure. The resulting compound, Azoveratridine, displays aqueous solubility, reversible photoisomerization, and light-dependent activity in neurons and myocardial slices.
Photocontrol of zebrafish behavior with a photoswitchable ligand of nicotinic acetylcholine receptors
(Elsevier B.V., 2026-07-03) Papotto, Claudio; Pérez Pérez, Nayeli Fernanda; Gomila Juaneda, Alexandre; Sortino, Rosalba; Cases, Mercè; Lee, Hyojung; Calzaferri, Francesco; Amici, Marco De; Dallanoce, Clelia; Gorostiza Langa, Pablo Ignacio; Matera, Carlo
The α7 nicotinic acetylcholine receptor (α7 nAChR) is a key modulator of neuronal and immunological signaling, and photopharmacology offers a route to control nicotinic transmission with high spatiotemporal precision. Here we report CPZ-2, a photoswitchable ligand inspired by a patented α7-active scaffold. CPZ-2 shows slow thermal relaxation, high photostability, and reversible photoswitching under one-photon irradiation, together with two-photon-induced photoisomerization monitored directly by HPLC–MS. Radioligand-binding competition performed on the trans-enriched state showed measurable displacement at α7 nAChRs and α1-containing receptors at 10 µM, with lower effects at α3β4 and α4β2 subtypes. Moreover, in wild-type zebrafish larvae, CPZ-2 modulated nicotine-evoked locomotion in a light-dependent manner after bath application. Finally, docking simulations in the α7 orthosteric site support a binding mode compatible with receptor engagement and suggest photostate-dependent differences in the orientation of the distal aromatic group relative to the C-loop region. Together, these data identify CPZ-2 as an uncharged, diffusible photoswitchable nicotinic ligand that combines robust one- and two-photon photochemistry with light-dependent modulation of nicotinic signaling in a wild-type vertebrate model.
Peptide-Functionalized Silicon-Photonic E‑Nose for Monitoring Oxidation in Extra Virgin Olive Oil
(American Chemical Society, 2026-03-24) Karami, Hamed; Pardo Martínez, Antonio; Fernández Romero, Luis; Rawal, Kaushal; Marco Colás, Santiago
Oxidation is a major factor affecting the quality and shelf life of Extra Virgin Olive Oil (EVOO), leading to chemical degradation and loss of freshness. This study investigates the assessment of EVOO freshness using a peptide-based optoelectronic nose (OE-nose) system combined with signal processing and machine learning techniques. Volatile organic compound (VOC) profiles from fresh and oxidized EVOO samples were acquired using a multigas sensor array implemented on the Aryballe NeOse Advance platform. The oxidation status of the samples was validated using reference chemical quality analyses. Sensor signals were subjected to baseline correction and normalization, without the application of digital smoothing. Full-sequence analysis was employed to exploit desorption-phase kinetics as a volatility-driven, implicit preseparation mechanism, enabling robust discrimination without chromatographic steps. Exploratory and supervised models were evaluated, including principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and support vector machines (SVM). The SVM model achieved a classification accuracy of 100%, while PLS-DA reached 95.8% accuracy under strict validation conditions. Compared to conventional analytical methods, the proposed approach offers a rapid, nondestructive, and cost-effective solution for on-site EVOO freshness evaluation. To the authors’ knowledge, this work represents the first application of a peptide-based optoelectronic nose for assessing EVOO oxidation, highlighting its potential advantages over conventional MOX- and polymer-based electronic nose systems reported in previous studies.
DNA Calorimetric Force Spectroscopy at Single Base Pair Resolution
(Nature Publishing Group, 2025-03-19) Rissone, Paolo; Rico Pastó, Marc; Smith, S. B.; Ritort Farran, Fèlix
DNA hybridization is a fundamental molecular reaction with wide-ranging applications in biotechnology. The knowledge of the temperature dependence of the thermodynamic parameters of duplex formation is crucial for quantitative predictions throughout the DNA stability range. It is commonly assumed that enthalpies and entropies are temperature independent, and heat capacity changes ΔCp equal zero. However, it has been known that this assumption is a poor approximation for a long time. Here, we combine single-DNA mechanical unzipping experiments using a temperature jump optical trap with a tailored statistical analysis to derive the ten heat-capacity change parameters of the nearest-neighbor model. Calorimetric force spectroscopy establishes a groundbreaking approach to studying nucleic acids that can be further extended to chemically modified DNA, RNA, and DNA/RNA hybrid structures.
The study of immunological markers in tuberculosis across animal models and its translation to human research
(2026-07-01) Díaz-Fernández, Sergio; Aleluia, Matilde; Saraiva, Margarida; Soldevilla, Pablo; Torrelles, Jordi B.; Sharan, Riti; Verreck, Frank A.W.; Izzo, Angelo; Vidal, Marta; Moreira, Ana C.; Pérez de Val, Bernat; Roca, Francisco Jose; Preda, Madalina; Torrents Serra, Eduard; Julián, Esther; Domínguez, José; Latorre, Irene
Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, remains one of the major causes of death from infection worldwide, with over a million associated deaths each year. The study of biomarkers for TB is critical for advancing our understanding and management of the disease. Biomarkers, defined as measurable indicators of biological states or conditions, are invaluable for the diagnosis, prognosis and treatment monitoring of TB. Clinical studies have provided critical knowledge on the matter but are also notoriously constrained by economical, ethical and sampling limitations. The use of animal models provides a simpler, more controllable, cost-effective setting with great potential for translation to humans. They also allow the evaluation of biomarkers within the respiratory compartment, when available, which is of particular interest due to the nature of TB pathogenesis. This Review focuses on the current landscape of TB biomarker discovery in several animal models, from invertebrates to large mammals. Here we summarize the basics of host–pathogen immune interaction, describe the main methodological approaches used and highlight the most substantial findings for each animal model studied. Furthermore, we discuss the advantages, challenges and limitations associated with species-specific differences in animal models. We conclude that integrating the data obtained from animal models and human studies is absolutely required to advance the TB field to accelerate the management of this disease.
Theory of Multiscale Epithelial Mechanics under Stretch: From Active Gels to Vertex Models
(American Physical Society, 2026-05-29) Ouzeri, Adam; Kale, Sohan; Chahare, Nimesh ; Torres Sánchez, Alejandro; Santos-Oliván, Daniel; Trepat Guixer, Xavier ; Arroyo, Marino
Epithelial monolayers perform a variety of mechanical functions, which include maintaining a cohesive barrier or developing three-dimensional (3D) shapes, while undergoing stretches over a wide range of magnitudes and loading rates. To perform these functions, they rely on a hierarchical organization, which spans molecules, cytoskeletal networks, adhesion complexes, and junctional networks up to the tissue scale. While the molecular understanding and ability to manipulate cytoskeletal components within cells is rapidly increasing, how these components integrate to control tissue mechanics is far less understood, partly due to the disconnect between theoretical models of subcellular dynamics and those at a tissue scale. To fill this gap, here we propose a formalism bridging active-gel models of the actomyosin cortex and 3D vertex-like models at a tissue scale. We focus on relatively short timescales or jammed tissues, such that tissue deformation is controlled by cellular deformations rather than by topological transitions of the junctional network. We show that this unified framework recapitulates a number of seemingly disconnected epithelial time-dependent phenomenologies, including stress relaxation following stretch-unstretch maneuvers, active flattening after buckling, or nonreciprocal and nonaffine pulsatile contractions. We further analyze tissue dynamics probed by a novel experimental setup operating in a pressure-controlled ensemble. Overall, the proposed framework systematically connects subcellular cortical dynamics and tissue mechanics and ties a variety of epithelial phenomenologies to a common subcellular origin.
Quatsome nanovesicles as antibacterial platform: Mechanistic insights into their activity against planktonic and biofilm Staphylococcus aureus
(Elsevier B.V., 2026-06-26) Korber, Mariana; Gallardo Moreno, Amparo M.; Ferrer Tasies, Lidia; Fernández Calderón, Maria Coronada; Pujol Solé, Nuria; Tomsen Melero, Judit; Guasch, Elba; Tamurejo Alonso, Purificación; Mitjans Arnal, Montserrat; Vinardell, María Pilar; Domingo Tafalla, Beatriu; Giannotti, Marina Inés; Rancan, Fiorenza; Schaudinn, Christoph; Veciana, Jaume; Ratera, Imma; Roldán, Mónica; González Mira, Elisabet; González Martín, María Luisa; Ventosa, Nora
The growing threat of antibiotic-resistant pathogens has intensified the demand for alternative antibacterial materials. Quatsomes-nanovesicles composed of cholesterol and quaternary ammonium surfactants (QAS)- emerge as promising candidates due to their intrinsic antimicrobial properties and tunable physicochemical characteristics. Here, we investigate the antibacterial activity of quatsomes incorporating QAS with either tetradecyl (C14) or hexadecyl (C16) alkyl chains against Staphylococcus aureus, a leading cause of hospital-acquired infections. Both quatsome types exhibited potent bactericidal activity in planktonic cultures, with C16containing formulations showing a 2.5-fold lower minimum bactericidal concentration than C14 counterparts. Confocal microscopy suggested a partial penetration of cationic quatsomes into the bacterial peptidoglycan layer, accompanied by significant increases in zeta-potential, suggesting strong electrostatic interactions without visible membrane disruption, as confirmed by scanning electron microscopy. Both formulations also demonstrated high efficacy against mature S. aureus biofilms, with no significant differences between alkyl chain lengths, indicating a mechanism primarily targeting the extracellular biofilm matrix. In addition, they showed a good antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). A preliminary safety assessment using reconstructed human epidermis (EpiskinTM) confirmed the non-irritant nature of both formulations. These findings highlight the potential of QAS-based quatsomes as effective and biocompatible nanocarriers for topical antibacterial applications, offering a promising platform for combating antibiotic-resistant infections in both planktonic and biofilm states.
Glycogen drives the sensory activation of POMC neurons
(Nature Publishing Group, 2026-05-27) Gómez-Valadés, Alicia G.; Meseguer, David; Varela, Luis; Lienhard, Gabriele; Fernández, Uxía; Vidal Itriago, Andrés; Toledo Soler, Miriam; Eyre, Elena; Laudo, Berta; Díaz Castro, Francisco; Pozo, Macarena; Boutagouga Boudjadja, Mehdi; Fos Domènech, Júlia; García Ramón, Pau; Ferreira, Mariana; Altirriba Gutiérrez, Jordi; Beiroa, Daniel; Chen, Bandy; Rodríguez Díaz, Amanda; Milà Guasch, Maria; Chivite, Íñigo; Obri, Arnaud; Ramírez, Sara; Haddad Tovolli, Roberta; Tahiri, Iasim; Gentry, Matthew S.; Agostino, Giuseppe D'; Nogueiras, Rubén; Renier, Nicolas; Horvath, Tamas L.; Guinovart, Joan J. (Joan Josep), 1947-2025; Duran Castells, Jordi; Schneeberger, Marc; Claret i Carles, Marc
Hypothalamic POMC neurons modulate systemic energy balance and glucose homeostasis by sensing nutritional state signals. In addition to this classic regulatory mode, these neurons are also activated by the sensory perception of food. Here, we report that food-related sensory cues engage glycogen metabolism in POMC neurons. Genetic depletion of glycogen through various approaches renders POMC neurons unresponsive to food-associated sensory stimuli. This defective perception of food is linked to alterations in consummatory behaviour, hepatic adaptations and cephalic insulin release associated with a prediabetic phenotype that progresses into overweight and overt diabetes with a high-calorie diet or ageing. Collectively, our results posit glycogen as a decisive fuel resource for meeting the rapid and demanding energy requirements linked with sensory activation. Furthermore, our data delineate the biological function of food perception and provide support for the physiological relevance of neuronal glycogen.
Late-stage modification of the alkaloid toxin veratridine to photocontrol excitable tissues.
(Elsevier Masson SAS, 2026-05-25) Camerin, Luisa ; Maleeva, Galyna ; Ramírez-Abreu, Ailín; Cilleros-Mañé, Víctor; Miftari, Drilon; Batlle, Montserrat ; Matera, Carlo ; Guasch Casany, Eduard; Gorostiza, Pau
Natural products and their structural derivatives have long played a crucial role in the discovery of new medical treatments and pharmacotherapies. However, certain natural compounds, such as toxins, are classified as hazardous substances that pose risk to human health. It is desirable to modulate the activity of toxins to minimize their harmful effects and unleash their potential as selective and bioavailable drugs. Yet, the functionalization of natural products remains a challenge due to their structural complexity. Here, we present two methods for late-stage C-H nitration and subsequent derivatization of the alkaloid steroidal neurotoxin veratridine, a sodium channel opener, by introducing an azobenzene photoswitch in its structure. The resulting compound, Azoveratridine, displays aqueous solubility, reversible photoisomerization, and light-dependent activity in neurons and myocardial slices.
Association of Breathing Effort With Survival in Patients With Acute Respiratory Distress Syndrome
(Lippincott, Williams & Wilkins, 2025-10) Parrilla-Gómez, Francisco José; Castellví, Andrea; Boutonnet, Víctor; Parrilla-Gómez, Andrés; Antolín Terreros, Marta; Mestre Somoza, Cristina; Blanes Bravo, Marina; Pratsobrerroca de la Rubia, Paola; Martín-López, Eva; Marco Colás, Santiago; Festa, Olimpia; Brochard, Laurent; Goligher, Ewan; Masclans Enviz, Joan Ramon
OBJECTIVES: Invasive mechanical ventilation (IMV) is crucial for acute respiratory distress syndrome (ARDS) management, but mortality remains high. While spontaneous breathing is key to weaning, excessive respiratory effort may injure the lung and diaphragm. Most existing data on respiratory effort during IMV are based on brief periods of observation, potentially underestimating the burden of inappropriate efforts. This study aims to characterize the evolution of respiratory effort over time in ARDS patients and its relation to survival. We hypothesized that nonsurvivors would spend a greater proportion of time in the high-effort range during the active breathing phase compared with survivors. DESIGN, SETTING, AND PATIENTS: In this prospective cohort study, we continuously recorded airway pressure, flow, esophageal, and gastric pressures in ARDS patients on mechanical ventilation during 7 days after the onset of spontaneous breathing. We analyzed physiologic respiratory effort variables, focusing on the proportion of time spent within defined effort ranges, and compared these data between ICU survivors and nonsurvivors. Statistical analysis was conducted using variance weighted methods to account for variability in the number of respiratory cycles analyzed per patient. This study is registered at ClinicalTrials.gov under identifier NCT06490523. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,485,405 respiratory cycles were analyzed from 26 ARDS patients (19 survivors, seven nonsurvivors). Nonsurvivors spent significantly more time in high effort (12% vs. 3%; p = 0.006). In contrast, survivors spent more time in the moderate-effort range (50% vs. 5%; p < 0.001). The time spend with high dynamic transpulmonary driving pressure (> 25 cm H2O) was also significantly different between groups (32% survivors vs. 74% nonsurvivors; p = 0.001). CONCLUSIONS: Patients who die of ARDS are more likely to be exposed to high respiratory effort for prolonged periods of time compared with survivors.
Cardiac fibroblast anisotropy is determined by YAP-dependent cellular contractility and ECM production
(Elsevier B.V., 2026-10) Pereira-Sousa, Daniel; Guillamat Bassedas, Pau; Niro, Francesco; Vinarsky, Vladimir; Fernandes, Soraia; Cassani, Marco; Pagliari, Stefania; Trepat Guixer, Xavier ; Rasponi, Marco; Oliver de la Cruz, Jorge; Forte, Giancarlo
Cardiac fibroblasts (CFbs) determine the topological arrangement and the anisotropy of the heart tissue which maintains tissue integrity and function through the production and remodeling of the extracellular matrix (ECM). Under pathological conditions, CFbs can activate into myofibroblasts and promote maladaptive ECM remodeling that may lead to heart failure. Yes-Associated Protein (YAP) - a key player in cardiac fibrosis onset - has been implicated in CFb activation but its role in coordinating the supracellular organization of CFbs and in shaping the instructive properties of the ECM remains poorly understood. We addressed these questions by generating CFbs from wild-type (WT) and YAP knockout (KO) human embryonic stem cells. YAP depletion reduced the expression of cardiogenic markers and altered the transcriptomic profile of ECM- and contractility-related genes. We further demonstrated that YAP expression is required for CFbs monolayer alignment, and its absence resulted in reduced ECM deposition, decreased anisotropy, and diminished force generation. Pharmacological inhibition of cell contractility closely mirrored YAP KO phenotype, suggesting that YAP regulates both monolayer organization and ECM structure through its control over contractility. ECM cross-seeding experiments confirmed the role of ECM as a structural guide for cellular alignment. Moreover, cardiomyocytes cultured on KO CFb-derived ECM exhibited impaired sarcomere organization and altered calcium dynamics. Together, these findings demonstrate that YAP activity in CFbs governs the structural and functional properties of the ECM, influencing both fibroblast alignment and cardiomyocyte activity. Moreover, they underscore the critical role of YAP in maintaining the supracellular organization and mechanical integrity of cardiac tissue.
Nanomotor-Assisted Intravesical Chemotherapy for Bladder Tumor Reduction and Suppression of Early Tumor Regrowth
(American Chemical Society, 2026-05-06) Vilaseca, Antoni; Llop Talaverón, Josep Manuel; Sánchez-López, Sònia; Fichna, Kristin; Crespo Cuadrado, Maria; Konuparamban, Acsah; Di Carlo, Valerio; Esporrín Ubieto, David; Macías Tarrío, Irene; Jutglar Soler, Oriol; Chen, Shuqin; Gómez Martínez, María; Bakenecker, Anna C.
Nanoparticles are widely used in nanomedicine for controlled drug delivery and improved bioavailability. However, their effectiveness is often limited by passive diffusion, especially in confined, fluid-filled environments like the bladder, where rapid drug clearance and uneven distribution reduce therapeutic impact. These challenges contribute to high recurrence in bladder cancer despite intravesical chemotherapy. To address this limitation, we present urease-powered nanomotors (NM) based on mesoporous silica nanoparticles loaded with Mitomycin C (MMC), the standard chemotherapeutic for nonmuscleinvasive bladder cancer. These NM useurea present in urine to induce motion and drug dispersion. In vitro, NM showed 2.3-fold higher uptake in mouse bladder cancer cells than passive nanoparticles and achieved the efficacy of free MMC (577.5 μg/mL) at a 20-fold lower dose (30 μg/mL). In vivo, a single intravesical dose reduced tumor volumes by 83% and prevented early tumor regrowth, demonstrating the potential of NM-based delivery for bladder cancer therapy.
Massively parallel quantification of mutational impact on IAPP amyloid formation
(Springer Nature, 2026-03-17) Badia Graset, Marta; Batlle Carreras, Cristina; Bolognesi, Benedetta
Amyloid fibrils formed by the islet amyloid polypeptide cause pancreatic beta-cell damage, resulting in reduced insulin secretion and type 2 diabetes. Changes in the amino acid sequence of this peptide can influence its aggregation rate, and animals expressing variants that do not form amyloids do not develop type 2 diabetes. Conversely, specific single amino acid changes can accelerate the aggregation rate of this peptide. Here, we employ deep mutational scanning to measure the ability of 1916 islet amyloid polypeptide variants, including substitutions, insertions, truncations and deletions, to nucleate amyloids. Our results identify a continuous stretch of residues from 15 to 32 that is particularly sensitive to mutation. This region, which is likely structured in amyloids, matches the core of the early aggregated species formed by this peptide in vitro. Within this region, mutations in residues 21 to 27 have a substantial effect, suggesting tighter structural constraints. Finally, we compare the mutational atlas of the islet amyloid polypeptide to that of amyloid beta - the peptide that aggregates in Alzheimer’s disease - and find that mutations that slow down nucleation correlate between the two amyloids, but mutations that accelerate nucleation in one amyloid cannot be used to predict mutational effects in the other.
Long-Distance Charge Transport between Cytochrome c and Complex III is Mediated by Protons and Reactive Oxygen Species
(Wiley-VCH, 2025-09-12) Lagunas, Anna; Gomila, Alexandre M. J.; Nin Hill, Alba; Guerra-Castellano, Alejandra; Pérez-Mejías, Gonzalo; Samitier i Martí, Josep; Rovira i Virgili, Carme; Rosa, Miguel A. de la; Díaz Moreno, Irene; Gorostiza Langa, Pablo Ignacio
Electron transfer (ET) between redox proteins is an essential process in the respiratory and photosynthetic transport chains. While intra-protein ET is well characterized, the experimental methods to investigate inter-protein ET are limited by the presence of the solvent and by the transient nature of the protein– protein interaction and ET event, which are averaged in protein ensembles. Wiring precisely oriented redox protein partners to the nanoscale electrodes of an electrochemical scanning tunneling microscope allows recording the time- and distance-dependence of the current flowing between them. These methods have revealed that the current flowing between individual protein pairs extends beyond tunneling distances and that it is electrochemically gated. However, the corresponding mechanism and the identity of the charge carriers in aqueous solution remain to be elucidated. To determine the species involved in long-distance charge transport between the redox partner proteins Cc and Cc1 of the respiratory chain, recordings are performed as a function of pH, in heavy water solutions, and in degassed solutions. It is observed that the spatial span and electrochemical gating of long-distance currents are reduced at high pH, in heavy water, and at low oxygen concentration, showing that the currents are assisted by superoxide anions and by protons.

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