118056 20240319080945.0 doi 10.3389/fcell.2022.912318 sideral 129348 ART-2022-129348 eng Aparicio-Yuste, Raúl Universidad de Zaragoza (orcid)0000-0003-4617-8130 A Stiff Extracellular Matrix Favors the Mechanical Cell Competition that Leads to Extrusion of Bacterially-Infected Epithelial Cells 2022 Access copy available to the general public Unrestricted Cell competition refers to the mechanism whereby less fit cells (“losers”) are sensed and eliminated by more fit neighboring cells (“winners”) and arises during many processes including intracellular bacterial infection. Extracellular matrix (ECM) stiffness can regulate important cellular functions, such as motility, by modulating the physical forces that cells transduce and could thus modulate the output of cellular competitions. Herein, we employ a computational model to investigate the previously overlooked role of ECM stiffness in modulating the forceful extrusion of infected “loser” cells by uninfected “winner” cells. We find that increasing ECM stiffness promotes the collective squeezing and subsequent extrusion of infected cells due to differential cell displacements and cellular force generation. Moreover, we discover that an increase in the ratio of uninfected to infected cell stiffness as well as a smaller infection focus size, independently promote squeezing of infected cells, and this phenomenon is more prominent on stiffer compared to softer matrices. Our experimental findings validate the computational predictions by demonstrating increased collective cell extrusion on stiff matrices and glass as opposed to softer matrices, which is associated with decreased bacterial spread in the basal cell monolayer in vitro. Collectively, our results suggest that ECM stiffness plays a major role in modulating the competition between infected and uninfected cells, with stiffer matrices promoting this battle through differential modulation of cell mechanics between the two cell populations. info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS info:eu-repo/grantAgreement/ES/MCIU/FPU20-05274 info:eu-repo/grantAgreement/ES/MICINN/PID2021-124271OB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.5 2022 DEVELOPMENTAL BIOLOGY 5 / 39 = 0.128 2022 Q1 T1 CELL BIOLOGY 66 / 191 = 0.346 2022 Q2 T2 1.418 2022 Developmental Biology 2022 Q1 Cell Biology 2022 Q2 6.3 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Muenkel, Marie Clark, Andrew G. Gómez-Benito, María J. Universidad de Zaragoza (orcid)0000-0002-1878-8997 Bastounis, Effie E. 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 10 (2022), 912318 [20 pp.] Frontiers in Cell and Developmental Biology 2296-634X 6955252 http://zaguan.unizar.es/record/118056/files/texto_completo.pdf Versión publicada 2345343 http://zaguan.unizar.es/record/118056/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:118056 articulos driver 2024-03-18-12:30:37 ARTICLE