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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.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.issn 2375-2548
dc.identifier.uri http://hdl.handle.net/10230/42205
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.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Science Advances. 2019;5(7):eaaw7243
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.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.identifier.doi http://dx.doi.org/10.1126/sciadv.aaw7243
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-69762R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-099718
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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