Measurements of molecular size and shape on a chip

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Xin Zhu - , University of Oxford (Autor:in)
  • Timothy J.D. Bennett - , University of Oxford (Autor:in)
  • Konstantin C. Zouboulis - , University of Oxford (Autor:in)
  • Dimitrios Soulias - , University of Oxford (Autor:in)
  • Michal Grzybek - , Zentrum für Membranbiochemie und Lipidforschung (Autor:in)
  • Justin L.P. Benesch - , University of Oxford (Autor:in)
  • Afaf H. El-Sagheer - , University of Southampton (Autor:in)
  • Ünal Coskun - , Zentrum für Membranbiochemie und Lipidforschung, Deutsches Zentrum für Diabetesforschung (DZD) e.V., Max Planck Institute of Molecular Cell Biology and Genetics, Paul Langerhans Institut Dresden (PLID) des Helmholtz Zentrum München (Autor:in)
  • Madhavi Krishnan - , University of Oxford (Autor:in)

Abstract

Size and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude and down to two carbon atoms in small molecules. We quantify the strength of molecular interactions across more than six orders of magnitude in affinity constant and track reactions in real time. Highly parallel measurements on individual molecules serve to characterize sample-state heterogeneity at the highest resolution, offering predictive input to model three-dimensional structure. We further leverage the method's structural sensitivity for diagnostics, exploiting ligand-induced conformational changes in the insulin receptor to sense insulin concentration in serum at the subnanoliter and subzeptomole scale.

Details

OriginalspracheEnglisch
Aufsatznummereadt5827
FachzeitschriftScience (New York, N.Y.)
Jahrgang388
Ausgabenummer6747
PublikationsstatusVeröffentlicht - 8 Mai 2025
Peer-Review-StatusJa

Externe IDs

Scopus 105008906198
ORCID /0000-0003-4375-3144/work/187998468
ORCID /0000-0003-2083-0506/work/187999963

Schlagworte

Schlagwörter

  • Humans, Insulin/blood, Lab-On-A-Chip Devices, Ligands, Molecular Weight, Protein Conformation, Receptor, Insulin/chemistry