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dc.contributor.authorDobramysl, Ulrichen
dc.contributor.authorPapoian, Garegin Aen
dc.contributor.authorErban, Radeken
dc.date.accessioned2016-03-17T13:58:13Z
dc.date.available2016-03-17T13:58:13Z
dc.date.issued2016-05-10en
dc.identifier.citationBiophysical Journal 2016 Volume 110, Issue 9, 10, Pages 2066–2075. DOI: 10.1016/j.bpj.2016.03.013en
dc.identifier.issn0006-3495
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/254553
dc.description.abstractFilopodia are ubiquitous fingerlike protrusions, spawned by many eukaryotic cells, to probe and interact with their environments. Polymerization dynamics of actin filaments, comprising the structural core of filopodia, largely determine their instantaneous lengths and overall lifetimes. The polymerization reactions at the filopodial tip require transport of G-actin, which enter the filopodial tube from the filopodial base and diffuse toward the filament barbed ends near the tip. Actin filaments are mechanically coupled into a tight bundle by cross-linker proteins. Interestingly, many of these proteins are relatively short, restricting the free diffusion of cytosolic G-actin throughout the bundle and, in particular, its penetration into the bundle core. To investigate the effect of steric restrictions on G-actin diffusion by the porous structure of filopodial actin filament bundle, we used a particle-based stochastic simulation approach. We discovered that excluded volume interactions result in partial and then full collapse of central filaments in the bundle, leading to a hollowed-out structure. The latter may further collapse radially due to the activity of cross-linking proteins, hence producing conical-shaped filament bundles. Interestingly, electron microscopy experiments on mature filopodia indeed frequently reveal actin bundles that are narrow at the tip and wider at the base. Overall, our work demonstrates that excluded volume effects in the context of reaction-diffusion processes in porous networks may lead to unexpected geometric growth patterns and complicated, history-dependent dynamics of intermediate metastable configurations.
dc.description.sponsorshiphe research leading to these results received funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement No. 239870. R.E. thanks the Royal Society for a University Research Fellowship, and the Leverhulme Trust for a Philip Leverhulme Prize (this prize money was used to support research visits of G.A.P. in Oxford). G.A.P. was supported by National Science Foundation grant No. CHE-1363081. U.D. was supported by a Junior Interdisciplinary Fellowship via Wellcome Trust grant No. 105602/Z/14/Z. This work was partially carried out during a visit by R.E. and U.D. to the Isaac Newton Institute. This work was partially supported by a grant from the Simons Foundation.
dc.languageengen
dc.language.isoenen
dc.publisherBiophysical Society
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rightsCreative Commons Attribution License 2.0 UK
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectActinsen
dc.subjectBiomechanical Phenomenaen
dc.subjectDiffusionen
dc.subjectModels, Biologicalen
dc.subjectProtein Multimerizationen
dc.subjectProtein Structure, Quaternaryen
dc.subjectPseudopodiaen
dc.titleSteric Effects Induce Geometric Remodeling of Actin Bundles in Filopodia.en
dc.typeArticle
prism.endingPage2075
prism.issueIdentifier9en
prism.publicationDate2016en
prism.publicationNameBiophysical Journalen
prism.startingPage2066
prism.volume110en
dc.rioxxterms.funderNSF
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.projectidCHE-1363081
dc.rioxxterms.projectid105602/Z/14/Z
dcterms.dateAccepted2016-03-09en
rioxxterms.versionofrecord10.1016/j.bpj.2016.03.013en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-05-10en
dc.contributor.orcidDobramysl, Ulrich [0000-0001-9363-654X]
dc.identifier.eissn1542-0086
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEPSRC (EP/K032208/1)
pubs.funder-project-idWELLCOME TRUST (105602/Z/14/Z)
cam.issuedOnline2016-03-13en
cam.orpheus.successThu Jan 30 12:54:49 GMT 2020 - Embargo updated*


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales