4D live imaging and computational modeling of a functional gut-on-a-chip evaluate how peristalsis facilitates enteric pathogen invasion
| Autor: | Aleix Boquet-Pujadas, Thomas Feaugas, Alba Petracchini, Alexandre Grassart, Héloïse Mary, Maria Manich, Samy Gobaa, Jean-Christophe Olivo-Marin, Nathalie Sauvonnet, Elisabeth Labruyère |
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| Přispěvatelé: | Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Intracellular Trafficking and Tissue Homeostasis, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Biomatériaux et Microfluidiques (plateforme) - Biomaterials and Microfluidics (platform), This project was funded by the Institut Pasteur through the 232 PTR grant Mechabiome. T.F. was a master’s student supported by the ASSU2000 fund, and A.P. was supported by Erasmus+ under the Unipharma program for recent graduates and by the PTR. The Bioimage Analysis Unit is supported by grants from the Labex IBEID (ANR-10-LABX-62-IBEID), France-BioImaging (ANR-10-INBS-04), and the PIA INCEPTION program (ANR-16-CONV-0005). The UTechS PBI is also supported by the French National Research Agency (France BioImaging, ANR-10–INBS–04, Investments for the Future). The work carried out at the Biomaterials and Microfluidics core facility was supported by a grant from the Institut Carnot Pasteur Microbes & Santé., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016) |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Science Advances Science Advances, 2022, 8 (42), ⟨10.1126/sciadv.abo5767⟩ |
| ISSN: | 2375-2548 |
| Popis: | Physical forces are essential to biological function, but their impact at the tissue level is not fully understood. The gut is under continuous mechanical stress because of peristalsis. To assess the influence of mechanical cues on enteropathogen invasion, we combine computational imaging with a mechanically active gut-on-a-chip. After infecting the device with either of two microbes, we image their behavior in real time while mapping the mechanical stress within the tissue. This is achieved by reconstructing three-dimensional videos of the ongoing invasion and leveraging on-manifold inverse problems together with viscoelastic rheology. Our results show that peristalsis accelerates the destruction and invasion of intestinal tissue by Entamoeba histolytica and colonization by Shigella flexneri . Local tension facilitates parasite penetration and activates virulence genes in the bacteria. Overall, our work highlights the fundamental role of physical cues during host-pathogen interactions and introduces a framework that opens the door to study mechanobiology on deformable tissues. |
| Databáze: | OpenAIRE |
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