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dc.contributor.authorYoung, LJen
dc.contributor.authorKaminski, Gabrieleen
dc.contributor.authorKaminski, Clemensen
dc.date.accessioned2018-04-26T10:08:11Z
dc.date.available2018-04-26T10:08:11Z
dc.date.issued2017-11-07en
dc.identifier.issn1463-9076
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/275181
dc.description.abstractThe major hallmark of Alzheimer’s disease is the deposition of plaques of amyloid fibrils formed from amyloid-beta (Ab) peptides. Kinetic studies have contributed significantly towards a mechanistic understanding of amyloid fibril self-assembly, however dynamic features of the aggregation process cannot be captured using ensemble methods. Here we present an assay for imaging Ab42 aggregation dynamics at the single fibril level, allowing for the quantitative extraction of concentration and temperature dependent kinetic parameters. From direct observation of elongation using TIRF and superresolution optical microscopy, we find that Ab42 fibril growth is strongly polarized, with fast and slow growing ends arising from different elongation rates, but also from a growth incompetent state, which dominates the process at the slow growing end. Our findings reveal the surprising complexity of the Ab42 fibril elongation reaction at the microscopic level.
dc.publisherRoyal Society of Chemistry
dc.titleImaging Aβ(1–42) fibril elongation reveals strongly polarised growth and growth incompetent statesen
dc.typeArticle
prism.endingPage27996
prism.publicationDate2017en
prism.publicationNamePhysical Chemistry Chemical Physicsen
prism.startingPage27987
prism.volume19en
dc.identifier.doi10.17863/CAM.22363
dcterms.dateAccepted2017-09-25en
rioxxterms.versionofrecord10.1039/c7cp03412aen
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-11-07en
dc.contributor.orcidKaminski, Gabriele [0000-0002-1843-2202]
dc.contributor.orcidKaminski, Clemens [0000-0002-5194-0962]
dc.identifier.eissn1463-9084
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MR/K02292X/1)
pubs.funder-project-idEPSRC (EP/L015889/1)
pubs.funder-project-idEPSRC (1108165)
pubs.funder-project-idWellcome Trust (203249/Z/16/Z)
pubs.funder-project-idEPSRC (EP/H018301/1)
pubs.funder-project-idMRC (MR/K015850/1)
pubs.funder-project-idBBSRC (BB/H023917/1)
pubs.funder-project-idMRC (G0902243)
pubs.funder-project-idWellcome Trust (089703/Z/09/Z)
pubs.funder-project-idEPSRC (EP/G037221/1)
cam.issuedOnline2017-10-03en
datacite.issupplementedby.doi10.1039/c7cp03412aen
rioxxterms.freetoread.startdate2018-10-03


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