Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area

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• dc.contributor.author Zhao, Runchen
• dc.contributor.author Afthinos, Alexandros
• dc.contributor.author Zhu, Tian
• dc.contributor.author Mistriotis, Panagiotis
• dc.contributor.author Li, Yizeng
• dc.contributor.author Serra Pascual, Selma A., 1981-
• dc.contributor.author Zhang, Yuqi
• dc.contributor.author Yankaskas, Christopher L.
• dc.contributor.author He, Shuyu
• dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
• dc.contributor.author Sun, Sean X.
• dc.contributor.author Konstantopoulos, Konstantinos
• dc.date.accessioned 2019-07-30T07:43:41Z
• dc.date.available 2019-07-30T07:43:41Z
• dc.date.issued 2019
• dc.description.abstract How cells sense hydraulic pressure and make directional choices in confinement remains elusive. Using trifurcating Ψ-like microchannels of different hydraulic resistances and cross-sectional areas, we discovered that the TRPM7 ion channel is the critical mechanosensor, which directs decision-making of blebbing cells toward channels of lower hydraulic resistance irrespective of their cross-sectional areas. Hydraulic pressure-mediated TRPM7 activation triggers calcium influx and supports a thicker cortical actin meshwork containing an elevated density of myosin-IIA. Cortical actomyosin shields cells against external forces and preferentially directs cell entrance in low resistance channels. Inhibition of TRPM7 function or actomyosin contractility renders cells unable to sense different resistances and alters the decision-making pattern to cross-sectional area-based partition. Cell distribution in microchannels is captured by a mathematical model based on the maximum entropy principle using cortical actin as a key variable. This study demonstrates the unique role of TRPM7 in controlling decision-making and navigating migration in complex microenvironments.
• dc.description.sponsorship This line of research was supported by the NIH through grants R01-CA183804 (to K.K.), U54-CA210173 (to K.K. and S.X.S.), and R01-GM114675 (to S.X.S. and K.K.), as well as by the Spanish Ministry of Economy and Competitiveness through grants SAF2015-69762R and RTI2018-099718 (to M.A.V.), and an institutional “Maria de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370 to M.A.V.) and FEDER funds (to M.A.V.).
• dc.format.mimetype application/pdf
• dc.identifier.citation Zhao R, Afthinos A, Zhu T, Mistriotis P, Li Y, Serra SA et al. Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area. Sci Adv. 2019;5(7):eaaw7243. DOI: 10.1126/sciadv.aaw7243
• dc.identifier.doi http://dx.doi.org/10.1126/sciadv.aaw7243
• dc.identifier.issn 2375-2548
• dc.identifier.uri http://hdl.handle.net/10230/42205
• dc.language.iso eng
• dc.publisher American Association for the Advancement of Science (AAAS)
• dc.relation.ispartof Science Advances. 2019;5(7):eaaw7243
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-099718
• dc.rights Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by-nc/4.0/
• dc.title Cell sensing and decision-making in confinement: The role of TRPM7 in a tug of war between hydraulic pressure and cross-sectional area
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion