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dc.contributor.authorFlagmeier, Patricken
dc.contributor.authorDe, Sumanen
dc.contributor.authorWirthensohn, Daviden
dc.contributor.authorLee, Stevenen
dc.contributor.authorVincke, Cen
dc.contributor.authorMuyldermans, Sen
dc.contributor.authorKnowles, Tuomasen
dc.contributor.authorGandhi, Sen
dc.contributor.authorDobson, Christopheren
dc.contributor.authorKlenerman, Daviden
dc.date.accessioned2017-08-04T09:02:03Z
dc.date.available2017-08-04T09:02:03Z
dc.date.issued2017-06-26en
dc.identifier.issn1433-7851
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265901
dc.description.abstractTo quantify and characterize the potentially toxic protein aggregates associated with neurodegenerative diseases, a high-throughput assay based on measuring the extent of aggregate-induced Ca(2+) entry into individual lipid vesicles has been developed. This approach was implemented by tethering vesicles containing a Ca(2+) sensitive fluorescent dye to a passivated surface and measuring changes in the fluorescence as a result of membrane disruption using total internal reflection microscopy. Picomolar concentrations of Aβ42 oligomers could be observed to induce Ca(2+) influx, which could be inhibited by the addition of a naturally occurring chaperone and a nanobody designed to bind to the Aβ peptide. We show that the assay can be used to study aggregates from other proteins, such as α-synuclein, and to probe the effects of complex biofluids, such as cerebrospinal fluid, and thus has wide applicability.
dc.languageengen
dc.language.isoenen
dc.publisherJohn Wiley & Sons Ltd.
dc.subjectAlzheimer's diseaseen
dc.subjectfluorescence imagingen
dc.subjectnano-scale biophysicsen
dc.subjectneurodegenerationen
dc.subjectprotein aggregationen
dc.titleUltrasensitive Measurement of Ca(2+) Influx into Lipid Vesicles Induced by Protein Aggregates.en
dc.typeArticle
prism.endingPage7754
prism.issueIdentifier27en
prism.publicationDate2017en
prism.publicationNameAngewandte Chemie - International Editionen
prism.startingPage7750
prism.volume56en
dc.identifier.doi10.17863/CAM.12271
dcterms.dateAccepted2017-04-19en
rioxxterms.versionofrecord10.1002/anie.201700966en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-06-26en
dc.contributor.orcidFlagmeier, Patrick [0000-0002-1204-5340]
dc.contributor.orcidDe, Suman [0000-0003-1675-0773]
dc.contributor.orcidWirthensohn, David [0000-0003-4403-9436]
dc.contributor.orcidLee, Steven [0000-0003-4492-5139]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.contributor.orcidKlenerman, David [0000-0001-7116-6954]
dc.identifier.eissn1521-3773
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (669237)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701013)
cam.issuedOnline2017-05-05en
rioxxterms.freetoread.startdate2018-05-05


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