My watch list


The first precise measurement of a single molecule's effective charge

Discovery could pave the way to new diagnostic tools

© Madhavi Krishnan / University of Zurich

Scientists can determine the effective electrical charge of a molecule by trapping it in a potential well by measuring how long it stays inside.

16-Jan-2018: For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve interactions between molecules like proteins, where their charge plays an essential role. Yet, the charge of a protein in an aqueous environment – its natural context in a living organism – is hard to determine accurately using traditional approaches.

Madhavi Krishnan, who holds an SNSF professorship at the University of Zurich, has developed a method to precisely measure the charge of a single molecule in solution. Her advance was described in a series of articles in Nature Nanotechnology, Physical Review E and the Journal of Chemical Physics. This discovery could pave the way to new diagnostic tools since, at a chemical level, many diseases are linked to a shift in a protein's electrical charge, which prevents the molecule from acting the way it should.

A molecule's electrical charge can be quite different in the gas phase and in solution. The reason for this difference lies in complex interactions between the object and the surrounding liquid. Hence, standard gas-phase measurements do not directly yield information on the molecule's behaviour in its biological context.

"Like kids kicking a ball"

Molecules in solution are in constant motion, randomly kicking each other. Krishnan and PhD student Francesca Ruggeri took advantage of this well-known phenomenon, called Brownian motion, in order to measure the effective charge of a molecule directly in solution.

First, they trapped the molecule in a "potential well". Rather than an actual well, this is a situation where the potential energy of the molecule is at its minimum. In such a situation, bouncing water molecules continuously attempt to expel the molecule from the well.

"It is like kids playing with a ball at the bottom of a pit," explains Krishnan. "The ball is the molecule we are interested in, and the children are the water molecules. The ball would have to receive quite a hard kick in order to fly out of the pit."

The higher the effective charge of the molecule, the greater the depth of the potential well and, consequently, the lower the likelihood that the molecule is ejected from the well. In practice, this means that the time needed for the molecule to be kicked out of the well is directly related to its effective charge.

"Ultimately it boils down to a statistical principle," explains Krishnan. "If we know how long a molecule remains trapped in the well, we know precisely how deep the well is. And since this depth depends directly on the molecule's effective charge, we can deduce this value very precisely too."

Two glass plates

In order to create a potential well, scientists compressed a solution containing the proteins between two glass plates, one of them being covered with microscopic holes. Molecules trapped in potential wells were labelled with fluorescent agents, which allowed them to be tracked with an optical microscope.

While the discovery has important fundamental implications, it could also pave the way towards novel diagnostic tools for many diseases caused by misshaped proteins, such as Alzheimer's and cancers. "We know that the 3D conformation of a protein influences its effective charge, and our work might present a novel route to detecting defective proteins."

Original publication:
F. Ruggeri et al.; "Single-molecule electrometry"; Nature Nanotechnology; 2017.
M. Krishnan; "A Simple Model for Electrical Charge in Globular Macromolecules and Linear Polyelectrolytes in Solution"; Journal of Chemical Physics; 2017.
F. Ruggeri and M. Krishnan; "Spectrally resolved single-molecule electrometry"; Journal of Chemical Physics; 2017.
F. Ruggeri and M. Krishnan; "Lattice diffusion of a single molecule in solution"; Physical Review E; 2017.

Facts, background information, dossiers

  • molecules
  • charge measurement
  • proteins
  • diagnostics

More about Universität Zürich

  • News

    How Type 1 Diabetes Gradually Destroys Insulin Production

    Using the new Imaging Mass Cytometry method, Zurich researchers have investigated the pancreas of healthy organ donors and those with type 1 diabetes. The study shows that many beta cells, which normally produce insulin, are still present in the early stages of the disease, but look very di ... more

    Insect Antibiotic Provides New Way to Eliminate Bacteria

    An antibiotic called thanatin attacks the way the outer membrane of Gram-negative bacteria is built. Researchers at the University of Zurich have now found out that this happens through a previously unknown mechanism. Thanatin, produced naturally by the spined soldier bug, can therefore be ... more

    Eco-Friendly Nanoparticles for Artificial Photosynthesis

    Researchers at the University of Zurich have developed a nanoparticle type for novel use in artificial photosynthesis by adding zinc sulfide on the surface of indium-based quantum dots. These quantum dots produce clean hydrogen fuel from water and sunlight – a sustainable source of energy. ... more

  • q&more articles

    From the reveller to the lark

    Because of their genes, some people come into the world either as a lark (early riser) or a night-owl (late sleeper). In addition, however, even in normal people, such ”chronotype“ changes with age. Starting at puberty they develop into revellers. At the age of 20 a change occurs and the ... more

  • Authors

    Dr. Steven A. Brown

    Steven B. Brown studied biochemistry at Harvard College, Cambridge, Massachusetts, USA. In 1997 he received his doctorate in the Department of Biological Chemistry and Molecular Pharmacology, Harvard University, Cambridge, Massachusetts, USA. From 1998 – 2005 he was a postdoctoral fellow at ... more

More about Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung

  • News

    The key to chemical transformations

    Chemist Xile Hu is the winner of the National Latsis Prize for 2017. Hu, a professor at the École Polytechnique Fédérale de Lausanne, was recognised for his outstanding scientific career and his original contributions to the fundamental understanding of catalysis. Catalysis is a field of ch ... more

    Liquid shock absorbers

    Remarkable liquid materials called colloids stiffen under impact. Researchers funded by the SNSF have studied the effect of powerful impacts such as those produced by firearms or micrometeorites. At first glance, colloids resemble homogeneous liquids such as milk or blood plasma. But in fa ... more

    Sodium and magnesium to replace lithium in batteries

    A project supported by the Swiss National Science Foundation (SNSF) aims to find new materials which can be used in rechargeable batteries and eventually provide alternatives to the current lithium batteries. Lithium-based batteries have several drawbacks, such as the limited availability o ... more

q&more – the networking platform for quality excellence in lab and process

The q&more concept is to increase the visibility of recent research and innovative solutions, and support the exchange of knowledge. In the broad spectrum of subjects covered, the focus is on achieving maximum quality in highly innovative sectors. As a modern knowledge platform, q&more offers market participants one-of-a-kind networking opportunities. Cutting-edge research is presented by authors of international repute. Attractively presented in a high-quality context, and published in German and English, the original articles introduce new concepts and highlight unconventional solution strategies.

> more about q&more

q&more is supported by:

Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE