Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators

Sergio Dominguez-Medina (1, 2) , Shawn Fostner (3) , Martial Defoort (3) , Marc Sansa (3) , Ann-Kathrin Stark (2) , Mohammad Abdul Halim (2) , Emeline Vernhes (4) , Marc Gély (3) , Guillaume Jourdan (3) , Thomas Alava (3) , Pascale Boulanger (5, 4) , Christophe D. Masselon (6, 2) , Sébastien Hentz (3)

1 BGE - UMR S1038 - Laboratoire de Biologie à Grande Échelle
2 UGA [2016-2019] - Université Grenoble Alpes [2016-2019]
3 CEA-LETI - Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information
4 I2BC - Institut de Biologie Intégrative de la Cellule
5 T5PHAG - Bactériophage T5
6 EDyP - Etude de la dynamique des protéomes

Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of ~30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

Sergio Dominguez-Medina, Shawn Fostner, Martial Defoort, Marc Sansa, Ann-Kathrin Stark, et al.. Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators. Science, 2018, 362 (6417), pp.918-922. ⟨10.1126/science.aat6457⟩. ⟨hal-02083419⟩