000120231 001__ 120231
000120231 005__ 20240319081024.0
000120231 0247_ $$2doi$$a10.1038/s41467-022-34701-y
000120231 0248_ $$2sideral$$a131178
000120231 037__ $$aART-2022-131178
000120231 041__ $$aeng
000120231 100__ $$aMcEvoy, E.
000120231 245__ $$aFeedback between mechanosensitive signaling and active forces governs endothelial junction integrity
000120231 260__ $$c2022
000120231 5060_ $$aAccess copy available to the general public$$fUnrestricted
000120231 5203_ $$aThe formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the regulation of endothelial junctions as dependent on the feedback between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Simulations reveal that active cell tension can stabilize cadherin bonds, but excessive RhoA signaling can drive bond dissociation and junction failure. While actin polymerization aids gap closure, high levels of Rac1 can induce junction weakening. Combining the modeling framework with experiments, our model predicts the influence of pharmacological treatments on the junction state and identifies that a critical balance between RhoA and Rac1 expression is required to maintain junction stability. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.
000120231 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C21
000120231 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000120231 590__ $$a16.6$$b2022
000120231 592__ $$a5.116$$b2022
000120231 591__ $$aMULTIDISCIPLINARY SCIENCES$$b6 / 73 = 0.082$$c2022$$dQ1$$eT1
000120231 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1
000120231 593__ $$aPhysics and Astronomy (miscellaneous)$$c2022$$dQ1
000120231 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1
000120231 594__ $$a24.9$$b2022
000120231 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000120231 700__ $$aSneh, T.
000120231 700__ $$aMoeendarbary, E.
000120231 700__ $$aJavanmardi, Y.
000120231 700__ $$aEfimova, N.
000120231 700__ $$aYang, C.
000120231 700__ $$aMarino-Bravante, G. E.
000120231 700__ $$aChen, X.
000120231 700__ $$0(orcid)0000-0001-8928-350X$$aEscribano, J.
000120231 700__ $$aSpill, F.
000120231 700__ $$0(orcid)0000-0002-9864-7683$$aGarcia-Aznar, J. M.$$uUniversidad de Zaragoza
000120231 700__ $$aWeeraratna, A. T.
000120231 700__ $$aSvitkina, T. M.
000120231 700__ $$aKamm, R. D.
000120231 700__ $$aShenoy, V. B.
000120231 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est.
000120231 773__ $$g13 (2022), 7089[14 pp.]$$tNature communications$$x2041-1723
000120231 8564_ $$s6795376$$uhttps://zaguan.unizar.es/record/120231/files/texto_completo.pdf$$yVersión publicada
000120231 8564_ $$s2441104$$uhttps://zaguan.unizar.es/record/120231/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000120231 909CO $$ooai:zaguan.unizar.es:120231$$particulos$$pdriver
000120231 951__ $$a2024-03-18-16:32:20
000120231 980__ $$aARTICLE