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DTSTART;TZID=Europe/Madrid:20261127T080000
DTEND;TZID=Europe/Madrid:20261127T170000
DTSTAMP:20261112T143226Z
CREATED:20261112T143226Z
LAST-MODIFIED:20261112T143226Z
UID:137512-1795766400-1795798800@ibecbarcelona.eu
SUMMARY:PhD Discussion. Ona Baguer and Dario Castellana
DESCRIPTION:Dual-Action 3D Biomaterial for radiotherapy: protection and regeneration of tissue during X-ray treatment\nDario Castellana\, Biomaterials for Regenerative Therapies \nRadiotherapy and ablative surgery are the standard of care for patients with head and neck squamous cell carcinoma. Radiation-based therapy can trigger side effects due to the ionizing beam\, which impair the patient’s quality of life. Amifostine is the only FDA-approved ROS-scavenging radioprotective drug\, but its clinical application is limited by suboptimal therapeutic effects under standard systemic delivery. We propose the application of a local delivery system to improve and extend the therapeutic window of the drug. A GelMA-based hydrogel embedding amifostine-loaded PLGA nanoparticles and calcium/zinc ionic nanoparticles can simultaneously protect the irradiated tissue and support the regeneration of resected areas. The radioprotective drug\, Amifostine\, was encapsulated in spherical PLGA nanoparticles (~250 nm) using a double-emulsion synthesis protocol. This approach generated amifostine nanoparticles (AMF NPs) achieving an encapsulation efficacy above 90%\, the nanoparticles were further embedded in a GelMA hydrogel\, controlling and tuning the drug release kinetics. To trigger and support the regeneration of new tissue\, a bottom-up protocol was developed to synthesize calcium- and zinc-based ionic nanoparticles (iNPs). The obtained iNPs were used to functionalize the surface of the GelMA hydrogel to promote a fast release of biological ions with angiogenic effects in the ablated tissue. The final delivery system was obtained upon crosslinking of a GelMA precursor solution enriched with amifostine-loaded PLGA NPs\, followed by surface modification with iNPs. The system can therefore sustain the fast release of iNPs from its surface and a controlled release of AMF-NPs from its matrix. In conclusion\, the proposed biomaterial will have a dual therapeutic effect: the rapid release of amifostine can reduce ROS concentration in the irradiated area\, while the sustained release of bioactive ions supports tissue regeneration and vascularization over time. \n  \nNuclear mechanics regulates the epithelial-mesenchymal transition in pancreatic cancer cells\nOna Baguer\, Cellular and Molecular Mechanobiology \nThe progression of pancreatic ductal adenocarcinoma (PDAC) is associated with the emergence of populations of cancer cells exhibiting both epithelial and mesenchymal features\, a state known as partial epithelial–mesenchymal transition (EMT). The EMT phenotypes are regulated by biochemical and mechanical cues from the tumour microenvironment\, including TGF-β signalling\, stromal stiffening and spatial constraints\, which can converge on shared signalling pathways. However\, how they interact to shape distinct EMT phenotypes remains poorly understood. To address this question\, we developed an in vitro system in which all three cues could be independently controlled: spatial constraints by micropatterning cells into circular colonies\, substrate stiffness by culturing colonies on gels with tunable stiffness\, and TGF-β signalling by adding TGF-β1 to the culture medium. Using a PDAC cell line with a weakly epithelial phenotype\, we analysed EMT markers alongside local mechanical features at the single-cell level and identified local cell density as a key regulator of EMT. Specifically\, local cell density regulated the expression of epithelial junctional markers and modulated TGF-β1-induced mesenchymal marker expression. In contrast\, substrate stiffness primarily promoted cell spreading and migration\, increasing the extent of low-density regions and thereby reshaping the spatial distribution of EMT phenotypes. These spatial differences were accompanied by changes in nuclear morphology\, pointing to a potential role for nuclear mechanics. Consistent with this\, lamin A/C knockdown\, which increases nuclear deformability\, enhanced mesenchymal features even in the absence of exogenous TGF-β1. Together\, these findings indicate that nuclear mechanics contributes to mediating the effects of mechanical and biochemical cues on EMT phenotypes\, providing insights into how the tumour microenvironment modulates cell plasticity.
URL:https://ibecbarcelona.eu/event/phd-discussion-ona-baguer-and-dario-castellana/
LOCATION:Sala 3 de Torre I\, PCB
CATEGORIES:IBEC Seminar
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DTSTART;TZID=Europe/Madrid:20270709T120000
DTEND;TZID=Europe/Madrid:20270709T130000
DTSTAMP:20261105T101324Z
CREATED:20261105T101324Z
LAST-MODIFIED:20261105T101324Z
UID:137424-1815134400-1815138000@ibecbarcelona.eu
SUMMARY:Ibec Seminar. Amin Doostmohammadi
DESCRIPTION:Multiscale dynamics and mechanics of the basement membrane in epithelial morphogenesis\nAmin Doostmohammadi\, Niels Bohr Institute\, University of Copenhagen\, Blegdamsvej 17\, 2100\, Copenhagen\, Denmark \nTissues must renew themselves throughout life. Cells divide to replace lost cells\, while damaged or unfit cells must be removed without breaking the tissue. Here we show that mechanics builds a landscape that guides both processes. \nWe first look at how cells flow in a growing layer. Using Lagrangian coherent structures\, we find attracting and repelling regions in the cell flow. These regions follow the stress hotspots in the tissue and predict where cells will be pushed out later. Cell motion alone can therefore reveal the mechanical state of the tissue. \nStress also decides where cells divide. In dense epithelia\, cell division follows the direction of greatest stress. This replaces the classic long axis rule\, which links division to cell shape. Each division relieves the stress that triggered it\, which creates a feedback loop that keeps the tissue in balance. We call this the principal stress rule. \nMechanics also decides which cells survive. When two cell types meet\, differences in force transmission decide the winner. Changing force transmission across cell junctions blocks the removal of dying cells\, and some extruded cells survive and invade soft gels. \nTogether\, these results show that a multicellular tissue steers its own renewal and removal through forces. The same landscape that places a cell also helps decide its fate. This view links active matter physics with tissue biology\, and it suggests new ways to control tissue growth\, repair\, and the spread of cancer cells.
URL:https://ibecbarcelona.eu/event/ibec-seminar-amin-doostmohammadi/
LOCATION:Sala Dolors Aleu\, Cluster II\, IBEC\, Baldiri i Reixac\, Barcelona
CATEGORIES:IBEC Seminar
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