https://hdl.handle.net/2072/478902 2026-04-06T22:14:13Z https://hdl.handle.net/2445/228016 Mapping mechanical stress in curved epithelia of designed size and shape Marín Llauradó, Ariadna; Kale, Sohan; Ouzeri, Adam; Golde, Tom; Sunyer Borrell, Raimon; Torres Sánchez, Alejandro; Latorre Ibars, Ernest; Gómez González, Manuel; Roca-Cusachs Soulere, Pere; Arroyo, Marino; Trepat Guixer, Xavier The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineer curved epithelial monolayers of controlled size and shape and map their state of stress. We design pressurized epithelia with circular, rectangular and ellipsoidal footprints. We develop a computational method, called curved monolayer stress microscopy, to map the stress tensor in these epithelia. This method establishes a correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we find pronounced stress anisotropies that impact cell alignment. Our approach enables a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions. 2026-03-11T16:43:06Z https://hdl.handle.net/2445/227772 Who arrived first? Priority effects on Candida albicans and Pseudomonas aeruginosa dual biofilms Arévalo Jaimes, Betsy Verónica; Admella, Joana; Torrents Serra, Eduard Historical processes in community assembly, such as species arrival order, influence interactions, causing priority effects. Candida albicans and Pseudomonas aeruginosa often co-occur in biofilm-based infections of the skin, lungs, and medical devices. Their predominantly antagonistic relationship involves complex physical and chemical interactions. However, the presence and implications of priority effects among these microorganisms remain largely unexplored. Here, we investigate the presence and impact of priority effect in dual-species biofilms using clinical isolates. By varying inoculation order, we observe significant changes in biofilm composition, structure, virulence, and antimicrobial susceptibility. The first colonizer has an advantage for surface colonization. Consecutive colonization increases biofilm virulence and negates C. albicans' protective effect on P. aeruginosa PAET1 against meropenem treatment. Finally, we propose N-acetylcysteine as an adjuvant for treating C. albicans and P. aeruginosa interkingdom infections, working independently of priority effects. 2026-03-02T15:26:35Z https://hdl.handle.net/2445/227658 Improving neuroblastoma therapy with a new p53 family-activating agent Almeida, Joana; Resende, Diana I. S. P.; Silva, R.; Villasante Bermejo, Aranzazu; Murphy, Catherine; Zingales, Veronica; Palmeira, Andreia; Skoda, Jan; Broso, Francesca; Vadivellu, Aiswariya; Oliveira, Paula A.; Reis, Salette; Nunes, Claudia; Loh, Amos H.P.; Ferreira, Joana Margarida; Martins, Eduarda P.; Costa, Bruno M.; Inga, Alberto; Samitier i Martí, Josep; Sousa, Emilia P.; Saraiva, Lucília Neuroblastoma (NB) is among the most common malignancies in children and represents a therapeutic challenge in pediatric oncology. p53 family proteins play a critical role in protecting cells from genomic instability and malignant transformation. However, in NB, their activities are often inhibited by interacting proteins such as MDM2. The interplay between p53 family pathway and N-Myc, a key biomarker of poor prognosis, is also a critical factor in NB pathogenesis. Herein, we disclose 1-(dibromomethyl)-3,4,6-trimethoxy-9H-xanthen-9-one (LEM3) as a new p53 family-activating agent with potent NB anticancer activity. At 0.13–2.1 μM, LEM3 inhibited the growth of several NB cell lines. Its activity was further evidenced in spheroids, patient-derived NB cells, and in a vasculature stiffness-based model of MYCN-amplified NB cells. This growth-inhibitory effect was associated with cell cycle arrest and apoptosis, in SH-SY5Y and SK-N-BE(2) NB cells, without apparent acquisition of resistance. LEM3 inhibited cell migration and invasion and reduced the expression of NB-related prognostic markers, particularly MYCN mRNA and protein levels. LEM3 released p53, TAp63, and TAp73 from their interaction with MDM2 both in a yeast-based assay and NB cells; for p53, this led to increased protein stabilization, DNA-binding ability, and transcriptional activity. Fluorescence quenching and docking analyses suggested that LEM3 binds to p53, TAp63, and TAp73 at the MDM2-binding site within their transactivation domain. LEM3 also synergies with doxorubicin and cisplatin in NB cells. Given the central role of the p53 family-MDM2-MYCN axis in NB pathogenesis, our findings support LEM3 as a promising compound for advancing NB targeted therapy. 2026-02-27T13:19:42Z https://hdl.handle.net/2445/224519 The minimal chemotactic cell Battaglia, Giuseppe; Borges Fernandes, Barbara; Apriceno, Azzurra; Arango-Restrepo, Andrés; Almadhi, Safa; Ghosh, Subhadip; Forth, Joe; López-Alonso, Jorge Pedro; Ubarretxena-Belandia, Iban; Rubi, José Miguel; Ruiz-Perez, Lorena; Williams, Ian The movement of cells and microorganisms in response to chemical gradients (chemotaxis) has played an essential role in the evolution of many biological processes. Cellular navigation works via the holistic assembly of numerous components into machineries that transform chemical energy into locomotion. Herein we present and discuss the minimal elements required for cell-like vesicles to be chemotactic. We show that lipid vesicles can propel themselves in response to chemical gradients when only a transmembrane protein and an encapsulated enzyme are incorporated into the vesicle structure. The herein proposed model serves as a proof of concept to show that even the simplest cell-like structure can experience chemotactic navigation. 2025-11-28T15:20:15Z