Journal Article

Quantitative mass imaging of single molecules

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

2018

Overview

The cellular processes underpinning life are orchestrated by proteins and their interactions. Investigating the structural and dynamic heterogeneity of proteins, despite being key to their function, and their interaction with drugs, poses a fundamental challenge to existing analytical and structural methodologies. We use interferometric scattering microscopy to mass-image single biomolecules in solution with less than 2% mass error, up to 19-kDa resolution, and 1-kDa precision. We resolve oligomeric distributions at high dynamic range, detect small-molecule binding, and mass-image proteins with associated lipids and sugars. These capabilities enable us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry provides spatially-resolved access to a broad range of biomolecular interactions, one molecule at a time.