Quantitative mass imaging of single biological macromolecules

Science. 2018 Apr 27;360(6387):423-427. doi: 10.1126/science.aar5839.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Amyloidogenic Proteins / chemistry
  • Humans
  • Interferometry / methods
  • Mass Spectrometry / methods
  • Microscopy, Interference / methods*
  • Polymerization*
  • Protein Aggregation, Pathological*
  • Proteins / chemistry*
  • Single Molecule Imaging / methods*
  • Spatio-Temporal Analysis

Substances

  • Actins
  • Amyloidogenic Proteins
  • Proteins