000118056 001__ 118056
000118056 005__ 20240319080945.0
000118056 0247_ $$2doi$$a10.3389/fcell.2022.912318
000118056 0248_ $$2sideral$$a129348
000118056 037__ $$aART-2022-129348
000118056 041__ $$aeng
000118056 100__ $$0(orcid)0000-0003-4617-8130$$aAparicio-Yuste, Raúl$$uUniversidad de Zaragoza
000118056 245__ $$aA Stiff Extracellular Matrix Favors the Mechanical Cell Competition that Leads to Extrusion of Bacterially-Infected Epithelial Cells
000118056 260__ $$c2022
000118056 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118056 5203_ $$aCell 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.
000118056 536__ $$9info:eu-repo/grantAgreement/EC/H2020/101018587/EU/Individual and Collective Migration of the Immune Cellular System/ICoMICS$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 101018587-ICoMICS$$9info:eu-repo/grantAgreement/ES/MCIU/FPU20-05274$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-124271OB-I00
000118056 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000118056 590__ $$a5.5$$b2022
000118056 592__ $$a1.418$$b2022
000118056 591__ $$aDEVELOPMENTAL BIOLOGY$$b5 / 39 = 0.128$$c2022$$dQ1$$eT1
000118056 593__ $$aDevelopmental Biology$$c2022$$dQ1
000118056 591__ $$aCELL BIOLOGY$$b66 / 191 = 0.346$$c2022$$dQ2$$eT2
000118056 593__ $$aCell Biology$$c2022$$dQ2
000118056 594__ $$a6.3$$b2022
000118056 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000118056 700__ $$aMuenkel, Marie
000118056 700__ $$aClark, Andrew G.
000118056 700__ $$0(orcid)0000-0002-1878-8997$$aGómez-Benito, María J.$$uUniversidad de Zaragoza
000118056 700__ $$aBastounis, Effie E.
000118056 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000118056 773__ $$g10 (2022), 912318 [20 pp.]$$tFrontiers in Cell and Developmental Biology$$x2296-634X
000118056 8564_ $$s6955252$$uhttps://zaguan.unizar.es/record/118056/files/texto_completo.pdf$$yVersión publicada
000118056 8564_ $$s2345343$$uhttps://zaguan.unizar.es/record/118056/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000118056 909CO $$ooai:zaguan.unizar.es:118056$$particulos$$pdriver
000118056 951__ $$a2024-03-18-12:30:37
000118056 980__ $$aARTICLE