Comunicacions a congressos (Física de la Matèria Condensada)
Permanent URI for this collectionhttps://hdl.handle.net/2445/226128
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OtherActive wetting of epithelial tissues.(American Society for Cell Biology, 2017-12-01) Pérez González, Carlos; Alert Zenón, Ricard; Blanch Mercader, Carles; Gómez González, Manuel; Kolodziej, Tomasz; Bazellières, Elsa; Casademunt i Viader, Jaume; Trepat Guixer, XavierDevelopment, regeneration and cancer involve changes in cell mechanical properties that lead to drastic transitions in tissue geometry and dimensionality. Given the fluid nature of living tissues, these transitions have been experimentally studied and theoretically modelled in terms of the physics of wetting phenomena, which describes how a fluid droplet spreads on a solid surface. However, physical forces, the effective determinants of tissue spreading, have never been measured in the context of tissue wetting. Here we perform a systematic study of tissue mechanics during epithelial wetting/dewetting. We induce a progressive expression of E‐cadherin in a confined monolayer of MDA‐MB‐231 cells and, simultaneously, we measure tissue forces using Traction Force Microscopy and Monolayer Stress Microscopy. The gradual formation of intercellular junctions produces a continuous increase in tissue contractility (pMLC), triggering a two‐fold increase in tissue forces that ends up in a spontaneous wetting‐dewetting transition. To understand how this transition arises from tissue active properties, we develop a wetting model based on active gels theory. Combining theory and experiments, we find that wetting‐dewetting transition results from a competition between contractility and traction forces, which introduces a new length scale, defining a critical size for tissue wetting. Strikingly, this implies that the critical tissue contractility driving the transition is dependent on tissue size, a phenomenon that has no counterpart in passive wetting/dewetting physics. Furthermore, we find that the critical tractions, which depend linearly on substrate ligand density, are the mechanical threshold for tissue spreading. Finally, we show that long‐wavelength morphological instabilities in our fluid interface, together with active fluctuations, explain tissue shape dynamics during dewetting. We conclude that tissue spreading can be understood as an active wetting transition of a viscous polar fluid.- Conference objectComputational reconstruction of the LDL-receptor-related protein 1 (LRP1) atomistic structure evolution from super-tertiary to quaternary(Biophysical Society, 2024) Tuveri, Gian Marco; Acosta Gutierrez, Silvia; Franzese, Giancarlo; Ruiz-Perez, Lorena; Battaglia, GiuseppeThe blood-brain barrier is a highly complex physiological barrier that separates the blood from the central nervous system to maintain the latter’s biological equilibrium. LDL receptor-related protein 1 (LRP1) is a receptor involved in BBB transcytosis and can be used by physiological or artificially induced processes. LRP1 is critical for the trafficking of misfolded proteins such as amyloid b, hyper-phosphorylated tau, and a-synuclein. Understanding its structure and function is essential to fully understanding neurological diseases like Alzheimer’s, Parkinson’s, Huntington’s, and other related dementias. LRP1 is a modular membrane protein composed of 4544 amino acids, around 1200 of which are involved in three long and flexible structures that contain coordinated calcium ions and are decorated with small sugar chains called glycans. These three flexible components are believed to have an active role in ligand binding activity and activate a peculiar and very efficient transport mechanism. No crystal structure of LRP1 is currently available. Here, we present two LRP1 conformers representing the extremes of a conformational spectrum ranging from a completely stretched, oligomer-like structure to a stable dimeric structure. The first is based on physical and biological considerations and has been built with the RoseTTAFold deep learning tool; the second conformer is obtained via homology modelling using the experimental observation of a homologous protein, LRP2, as template. We aim to assess the two conformers’ free energy variation considering the dynamics of the flexible domains obtained with atomistic molecular dynamics while rigidly fixing b-propellers’ coordinates. The obtained conformations are solvated with the BF method to estimate the species’ free energy of solvation.
- Conference objectOptimal collective durotaxis through E-cadherin adhesions(American Society for Cell Biology, 2023-02-01) Fuente, Jesús M. de la; Sunyer, Raimon; Pallarès, Macià Esteve; Pi Jaumà, Irina; Fortunato, Isabela Corina Santos; Grazu, Valeria; Gómez González, Manuel; Roca-Cusachs Soulere, Pere; Alert Zenón, Ricard; Casademunt i Viader, Jaume; Trepat Guixer, XavierThe directed migration of cellular clusters enables morphogenesis, wound healing, and collective cancer invasion. Gradients of substrate stiffness are known to direct the migration of cellular clusters in a process called collective durotaxis, but underlying mechanisms remain unclear. Durotaxis has been mainly studied when mediated by focal adhesions at the extracellular matrix (ECM) interface. However, in ECM-depleted environments cells migrate through the cell-cell adhesion protein E-cadherin. Here we show that when cell adhesion is mediated by E-Cadherin, clusters of cancer cells dewet on soft substrates and wet on stiff ones. At intermediate stiffness, clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient, and actomyosin activity. We first demonstrate this new migratory mode on substrates coated with E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop a physical model of three-dimensional active wetting that explains this mode of collective durotaxis in terms of a balance between in-plane active traction and tissue contractility, and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a new physical mechanism of collective durotaxis, through both cell-cell and cell-substrate adhesion ligands, based on the wetting properties of active droplets.
- Conference objectMapping the structure and function of whole-mount retinal organoids(Association for Research in Vision and Ophthalmology, 2024-06) Cunquero, Marina; Isla-Magrane, Helena; Castro-Olvera, Gustavo; Soriano i Fradera, Jordi; Marsal, Maria; Mateos, Nicolas; Zufiaurre, Maddalen; Garcia-Arumi, Josep; Duarri, Anna; Loza-Alvarez, PabloCell therapy is a therapeutic avenue for retinal degenerative diseases. Photoreceptortransplantation faces challenges in obtaining high-quality and mature photoreceptors that caneffectively integrate and function, facilitating regeneration. For designing therapies we will produceretinal organoids (RO) from ihPSC. To enhance our understanding of RO maturation in a 3D anddynamic context, we aim to characterize the structure and function of retinal neurons. This will helpidentifying the optimal timing for harvesting photoreceptors for subsequent implantation. In thiswork, we focus on the characterization of RO derived from ihPSC from healthy and vision-impairedindividuals, specifically Retinitis Pigmentosa type 25. We tracked calcium activity in 3D with light-sheet fluorescence microscopy (LSFM). Thisoptical configuration allows fast tracking of dynamics (10 Z-planes at 5 Hz) occurring on a volumetricscale (600x830x100μm) with minor photo-toxic effects. For visualizing changes in the calciuminfluxes, we used viral vectors encoding for GCaMP6s. Changes in fluorescence intensity werequantified and analysed in a 3D fashion to determine the pattern and frequency of calcium waves inthe neuronal network. Subsequently to the life dynamic recordings, and to characterize thestructure of whole-mount mature ROs (up to day 250), we optimized an optical clearing method(FluoClear BABB) in combination with improved antibody permeabilization. We imaged in high-resolution the calcium activity of RO derived from healthy and vision-impaired donors and quantified differences in the functional communities of neurons by usingtransfer entropy. Using our clearing protocol, we identified the morphology and population of thethree neuron-path that provide the direct route for visual information transmission: cone and rodphotoreceptors, bipolar and ganglion cells. RO are promising in vitro models for studying retinal diseases. Our findings shed morelight on the temporal, spatial and functional organization of retinal cells within the organoid. Our LSFM can be applied to study fast events occurring in mm range samples with cellular resolution