Another big step towards understanding the electric properties of the cell

Having measured the electric polarizability of DNA – a fundamental property that directly influences its biological functions – for the first time ever last year, IBEC´s Nanoscale Bioelectrical Characterization group has made a further breakthrough in the understanding of the dielectric properties of cell constituents by measuring the electric polarizability of the main components of the cell membrane – namely lipids, sterols and proteins – with a spatial resolution down to 50nm.

The cell membrane plays an essential role in fundamental bioelectric phenomena. Found in places such as neurons or cardiac cells, it regulates the exchange of ions between the cell and the environment, as well as enabling the formation of electric potentials that can propagate over long distances.

It also largely determines cell response to externally applied electrical fields, determining the effects of these fields on the cell function or the possibility to electrically manipulate single cells by means of electrokinetic techniques. In all these processes, a key physical property is the electrical polarizability of the cell membrane, i.e. how the membrane’s electrical dipoles orient in response to an electric field. Now, IBEC’s Nanoscale Bioelectrical Characterization group has developed a technique to access to this property with an unprecedented spatial resolution.

To achieve their aim, which was published in the journal Nanoscale this week, the researchers increased the sensitivity and accuracy of a methodology they developed over the years at IBEC, which is based on electrostatic force microscopy (EFM), to enable its use with insulating substrates such as mica or glass, which are common in biomembrane research. This technique enables them not only to explore the morphology of small scale biological complexes, but also to measure their electric polarizability for the first time ever. By revealing this inherent electrical property that makes each biomembrane unique, researchers can now realistically predict the electrical functionality of these cell constituents and gain a new understanding of the essential role they play in our bodies.

“Until now, existing techniques have only measured the electric polarizability of biomembranes with a spatial resolution of several micrometres, thus losing the information corresponding to their ultrastructure,” says group leader Gabriel Gomila. “Our success in measuring biomembranes that are only 5 nm thick with a spatial resolution down to 50 nm opens nanoscale dielectric characterization to access the local electrical properties of any type of biomembrane.” As an example, the researchers provided the electrical polarizability properties of biomembranes made of proteins, lipids and cholesterol, which are the main components of natural cell membranes.

“With this work we pushed the capabilities of a technique developed over the years here at IBEC even further forward, and every time we are closer to reaching the single molecule limit,” says Laura Fumagalli, a former member of the group now at the University of Manchester. “Here we’ve reached the limit of hundreds of molecules and predict the capability to reach the single biomolecule limit in the near future.”

In addition, this achievement could open the door to the development of a new label-free nanoscale biomembrane characterization method based on the local dielectric response, similar to one the researchers developed already for single nanoparticles and viruses, which may answer fundamental questions on how cell membranes are organized at the smallest scales.

Aurora Dols-Perez, Georg Gramse, Annalisa Calo, Gabriel Gomila and Laura Fumagalli (2015). Nanoscale electric polarizability of ultrathin biolayers on insulator substrates by electrostatic force microscopy. Nanoscale, epub ahead of print