452620 Measuring Macromolecular Properties in a Field-Free Single Molecule Trap

Wednesday, November 16, 2016: 4:15 PM
Embarcadero (Parc 55 San Francisco)
Madhavi Krishnan, Departments of Chemistry & Physics, University of Zurich, Zurich, Switzerland

Mass and electrical charge are fundamental properties of biological macromolecules.
While molecular mass has long been determined with atomic precision, we have
achieved for the first time a high-precision (< 1 e), absolute measurement of the
electrical charge of molecules such as nucleic acid oligomers, and globular and
intrinsically disordered proteins in solution. The method is based on parallel, external
field-free trapping of nanometer-scale entities in the fluid phase (1,2), requires one
molecule, is rapid, and also facilitates an estimate of a dielectric coefficient of the
molecular interior. We have further demonstrated direct detection of chemical
modifications and single point mutations in proteins. Since net macromolecular
charge strongly depends on 3D conformation, high precision electrometry will serve
as a new approach to probe molecular structure, dynamics and interactions in
solution, down to the level of the single molecule and in real time. The ability to
experimentally link electrical charge and molecular structure will likely open up an
unexplored physical dimension in biology.


(1) Krishnan, M., Mojarad, N., Kukura, P. & Sandoghdar, V. Geometry-induced
electrostatic trapping of nanometric objects in a fluid.
Nature 467, 692-695 (2010).
(2) Mojarad, N. & Krishnan, M. Measuring the size and charge of single nanoscale
objects in solution using an electrostatic fluidic trap. Nature Nanotechnology 7,
448-452 (2012).

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