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Membrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure.

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cam.issuedOnline2021-11-12
cam.orpheus.counter1
cam.orpheus.successMon Nov 22 07:30:23 GMT 2021 - Embargo updated
datacite.isderivedfrom.doi10.1101/2021.07.11.451603
dc.contributor.authorMorzy, Diana
dc.contributor.authorJoshi, Himanshu
dc.contributor.authorSandler, Sarah E
dc.contributor.authorAksimentiev, Aleksei
dc.contributor.authorKeyser, Ulrich F
dc.contributor.orcidMorzy, Diana [0000-0001-5909-2876]
dc.contributor.orcidJoshi, Himanshu [0000-0003-0769-524X]
dc.contributor.orcidSandler, Sarah E [0000-0001-9689-8684]
dc.contributor.orcidAksimentiev, Aleksei [0000-0002-6042-8442]
dc.contributor.orcidKeyser, Ulrich F [0000-0003-3188-5414]
dc.date.accessioned2021-11-09T00:30:13Z
dc.date.available2021-11-09T00:30:13Z
dc.date.issued2021-11-24
dc.description.abstractDNA nanotechnology has emerged as a promising method for designing spontaneously inserting and fully controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based membrane channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications can cause fraying of terminal base pairs of nicked DNA constructs, distorting them when embedded in a lipid bilayer. Importantly, we show that DNA nanostructures with no backbone discontinuities form more stable conductive pores and insert into membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows design and maintenance of membrane-spanning helices in a tilted orientation within the lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.
dc.description.sponsorshipWinton Programme for the Physics of Sustainability EPSRC Scholarship (1948702). EPSRC Cambridge NanoDTC (EP/S022953/1) ERC consolidator grant (DesignerPores 647144) National Science Foundation USA (DMR-1827346) XSEDE allocation grant (MCA05S028) Leadership Resource Allocation (MCB20012)
dc.identifier.doi10.17863/CAM.77902
dc.identifier.eissn1530-6992
dc.identifier.issn1530-6984
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330458
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Chemical Society (ACS)
dc.publisher.urlhttp://dx.doi.org/10.1021/acs.nanolett.1c03791
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.subjectDNA structures
dc.subjectlipid membranes
dc.subjectnicks
dc.subjectprotein-mimicking
dc.subjectsynthetic ion channel
dc.subjecttilt
dc.subjectDNA
dc.subjectIon Channels
dc.subjectLipid Bilayers
dc.subjectNanostructures
dc.subjectNanotechnology
dc.titleMembrane Activity of a DNA-Based Ion Channel Depends on the Stability of Its Double-Stranded Structure.
dc.typeArticle
dcterms.dateAccepted2021-11-04
prism.publicationDate2021
prism.publicationNameNano Lett
pubs.funder-project-idEuropean Research Council (647144)
pubs.funder-project-idEPSRC (1948702)
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/S022953/1)
rioxxterms.licenseref.startdate2021-11-12
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1021/acs.nanolett.1c03791

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