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dc.contributor.authorHaley, Kathryn
dc.contributor.authorKronenberg, Nils Michael
dc.contributor.authorLiehm, Philipp
dc.contributor.authorElshani, Mustafa
dc.contributor.authorBell, Cameron
dc.contributor.authorHarrison, David James
dc.contributor.authorGather, Malte Christian
dc.contributor.authorReynolds, Paul Andrew
dc.date.accessioned2018-07-03T10:14:03Z
dc.date.available2018-07-03T10:14:03Z
dc.date.issued2018-06-27
dc.identifier.citationHaley , K , Kronenberg , N M , Liehm , P , Elshani , M , Bell , C , Harrison , D J , Gather , M C & Reynolds , P A 2018 , ' Podocyte injury elicits loss and recovery of cellular forces ' Science Advances , vol. 4 , no. 6 , eaap8030 . https://doi.org/10.1126/sciadv.aap8030en
dc.identifier.issn2375-2548
dc.identifier.otherPURE: 253025665
dc.identifier.otherPURE UUID: 2a145dc3-5ac1-41f2-a3bb-7f0cdd8658ca
dc.identifier.otherScopus: 85049212201
dc.identifier.otherORCID: /0000-0001-8738-1245/work/46362067
dc.identifier.otherORCID: /0000-0002-4857-5562/work/47136469
dc.identifier.otherWOS: 000443175500014
dc.identifier.urihttp://hdl.handle.net/10023/14836
dc.descriptionK.E. Haley was funded by a University of St. Andrews 600th Anniversary PhD Scholarship. M.C.G. acknowledges support by the Human Frontiers Science Program (RGY0074/2013), the Scottish Funding Council (via SUPA), EPSRC (EP/P030017/1) and the ERC Starting Grant ABLASE (640012). D.J.H. was supported by NHS Lothian. M.C.G. and P.A.R. acknowledge support by the BBSRC (BB/P027148/1).en
dc.description.abstractIn the healthy kidney, specialized cells called podocytes form a sophisticated blood filtration apparatus that allows excretion of wastes and excess fluid from the blood while preventing loss of proteins such as albumin. To operate effectively, this filter is under substantial hydrostatic mechanical pressure. Given their function, it is expected that the ability to apply mechanical force is crucial to the survival of podocytes. However, to date podocyte mechanobiology remains poorly understood, largely due to a lack of experimental data on the forces involved. Herein, we perform quantitative, continuous, non-disruptive and high-resolution measurement of the forces exerted by differentiated podocytes in real time using a recently introduced functional imaging modality for continuous force mapping. Using an accepted model for podocyte injury, we find that injured podocytes experience near complete loss of cellular force transmission, but that this is reversible under certain conditions. The observed changes in force correlate with F-actin rearrangement and reduced expression of podocyte-specific proteins. By introducing robust and high-throughput mechanical phenotyping and by demonstrating the significance of mechanical forces in podocyte injury, this research paves the way to a new level of understanding of the kidney. In addition, we integrate cellular force measurements with immunofluorescence and perform continuous long-term force measurements of a cell population, which has not been feasible with established force mapping techniques. As such, our approach has general applicability to a wide range of biomedical questions involving mechanical forces.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofScience Advancesen
dc.rightsCopyright © 2018 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 License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectRB Pathologyen
dc.subjectDASen
dc.subject.lccRBen
dc.titlePodocyte injury elicits loss and recovery of cellular forcesen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.School of Physics and Astronomyen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1126/sciadv.aap8030
dc.description.statusPeer revieweden
dc.date.embargoedUntil2018-06-27


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