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Quantitative mass imaging of single biological macromolecules

Quantitative mass imaging of single biological macromolecules
Quantitative mass imaging of single biological macromolecules

The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.

0036-8075
423-427
Young, Gavin
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Hundt, Nikolas
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Cole, Daniel
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Fineberg, Adam
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Andrecka, Joanna
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Tyler, Andrew
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Olerinyova, Anna
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Ansari, Ayla
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Marklund, Erik G.
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Collier, Miranda P.
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Chandler, Shane A.
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Tkachenko, Olga
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Allen, Joel
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Crispin, Max
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Billington, Neil
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Takagi, Yasuharu
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Sellers, James R.
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Eichmann, Cédric
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Selenko, Philipp
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Frey, Lukas
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Riek, Roland
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Galpin, Martin R.
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Struwe, Weston B.
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Benesch, Justin L.P.
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Kukura, Philipp
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Young, Gavin
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Hundt, Nikolas
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Cole, Daniel
4fe2ef33-a304-4814-bef2-a2630ebb1497
Fineberg, Adam
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Andrecka, Joanna
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Tyler, Andrew
392fb188-e7cb-49f5-b3c3-9231fc501f44
Olerinyova, Anna
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Ansari, Ayla
30584b3b-a5ad-4011-8e0a-e625ce2a5f48
Marklund, Erik G.
186200a2-3aca-4598-bbb6-94c8a0129ee9
Collier, Miranda P.
1be36126-d2e8-4d66-841c-042fd38f7152
Chandler, Shane A.
9617bd34-6ea8-4fa1-9819-9bc05b558106
Tkachenko, Olga
fef4bf1e-d853-4d23-a4a2-6cef1f3567b4
Allen, Joel
c873d886-2a66-475b-ae04-57a10b37e716
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Billington, Neil
9c88f1d6-1e2f-491f-8bf0-1a747fccf095
Takagi, Yasuharu
00330c0b-41c4-4d03-8ded-477d875c1bd4
Sellers, James R.
65ff0b53-4a24-4968-b446-7a24d2f55532
Eichmann, Cédric
538c8696-0a0c-409c-93ac-073928c440de
Selenko, Philipp
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Frey, Lukas
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Riek, Roland
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Galpin, Martin R.
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Struwe, Weston B.
16a348b1-3921-4a2d-b5fb-d341fccea65f
Benesch, Justin L.P.
9bdc06a0-68d0-48f0-89d3-fd5baff7168b
Kukura, Philipp
810f67d1-a172-4623-86ce-4769262a3b6f

Young, Gavin, Hundt, Nikolas, Cole, Daniel, Fineberg, Adam, Andrecka, Joanna, Tyler, Andrew, Olerinyova, Anna, Ansari, Ayla, Marklund, Erik G., Collier, Miranda P., Chandler, Shane A., Tkachenko, Olga, Allen, Joel, Crispin, Max, Billington, Neil, Takagi, Yasuharu, Sellers, James R., Eichmann, Cédric, Selenko, Philipp, Frey, Lukas, Riek, Roland, Galpin, Martin R., Struwe, Weston B., Benesch, Justin L.P. and Kukura, Philipp (2018) Quantitative mass imaging of single biological macromolecules. Science, 360 (6387), 423-427. (doi:10.1126/science.aar5839).

Record type: Article

Abstract

The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.

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Young_Science_2018_PubMed_Central - Accepted Manuscript
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Accepted/In Press date: 26 March 2018
e-pub ahead of print date: 27 April 2018

Identifiers

Local EPrints ID: 421195
URI: http://eprints.soton.ac.uk/id/eprint/421195
ISSN: 0036-8075
PURE UUID: 7c434088-cc75-4438-810c-9d96de012bb7
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 24 May 2018 16:30
Last modified: 07 Oct 2020 02:15

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Contributors

Author: Gavin Young
Author: Nikolas Hundt
Author: Daniel Cole
Author: Adam Fineberg
Author: Joanna Andrecka
Author: Andrew Tyler
Author: Anna Olerinyova
Author: Ayla Ansari
Author: Erik G. Marklund
Author: Miranda P. Collier
Author: Shane A. Chandler
Author: Olga Tkachenko
Author: Joel Allen
Author: Max Crispin ORCID iD
Author: Neil Billington
Author: Yasuharu Takagi
Author: James R. Sellers
Author: Cédric Eichmann
Author: Philipp Selenko
Author: Lukas Frey
Author: Roland Riek
Author: Martin R. Galpin
Author: Weston B. Struwe
Author: Justin L.P. Benesch
Author: Philipp Kukura

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