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dc.contributor.authorHakala, Tuuli A
dc.contributor.authorYates, Emma V
dc.contributor.authorChalla, Pavan
dc.contributor.authorToprakcioglu, Zenon
dc.contributor.authorNadendla, Karthik
dc.contributor.authorMatak-Vinkovic, Dijana
dc.contributor.authorDobson, Christopher M
dc.contributor.authorMartínez, Rodrigo
dc.contributor.authorCorzana, Francisco
dc.contributor.authorKnowles, Tuomas
dc.contributor.authorLopes Bernardes, Goncalo
dc.date.accessioned2021-09-16T23:30:46Z
dc.date.available2021-09-16T23:30:46Z
dc.date.issued2021-10-13
dc.identifier.issn0002-7863
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/328148
dc.description.abstractBiomimetics is a design principle within chemistry, biology, and engineering, but chemistry biomimetic approaches have been generally limited to emulating nature's chemical toolkit while emulation of nature's physical toolkit has remained largely unexplored. To begin to explore this, we designed biophysically mimetic microfluidic reactors with characteristic length scales and shear stresses observed within capillaries. We modeled the effect of shear with molecular dynamics studies and showed that this induces specific normally buried residues to become solvent accessible. We then showed using kinetics experiments that rates of reaction of these specific residues in fact increase in a shear-dependent fashion. We applied our results in the creation of a new microfluidic approach for the multidimensional study of cysteine biomarkers. Finally, we used our approach to establish dissociation of the therapeutic antibody trastuzumab in a reducing environment. Our results have implications for the efficacy of existing therapeutic antibodies in blood plasma as well as suggesting in general that biophysically mimetic chemistry is exploited in biology and should be explored as a research area.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Chemical Society (ACS)
dc.rightsAll rights reserved
dc.titleAccelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.
dc.typeArticle
prism.endingPage16410
prism.issueIdentifier40
prism.publicationDate2021
prism.publicationNameJ Am Chem Soc
prism.startingPage16401
prism.volume143
dc.identifier.doi10.17863/CAM.75603
dcterms.dateAccepted2021-09-09
rioxxterms.versionofrecord10.1021/jacs.1c03681
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10-04
dc.contributor.orcidHakala, Tuuli A [0000-0002-2075-3451]
dc.contributor.orcidChalla, Pavan [0000-0002-0863-381X]
dc.contributor.orcidToprakcioglu, Zenon [0000-0003-1964-8432]
dc.contributor.orcidMartínez, Rodrigo [0000-0002-5850-8494]
dc.contributor.orcidCorzana, Francisco [0000-0001-5597-8127]
dc.contributor.orcidKnowles, Tuomas [0000-0002-7879-0140]
dc.contributor.orcidLopes Bernardes, Goncalo [0000-0001-6594-8917]
dc.identifier.eissn1520-5126
rioxxterms.typeJournal Article/Review
pubs.funder-project-idRoyal Society (URF\R\180019)
pubs.funder-project-idEuropean Research Council (337969)
pubs.funder-project-idEuropean Commission (EC) (852985)
cam.issuedOnline2021-10-04
cam.orpheus.successMon Oct 11 07:30:37 BST 2021 - Embargo updated
cam.orpheus.counter3
rioxxterms.freetoread.startdate2022-10-04


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