Detect Membrane Changes with Neutrons

New method for drug research

cell membranes
Membrane-active agents such as benzocaine (green) can become embedded in lipid bilayers and change their structure. Neutron studies are ideal for detecting such changes. Copyright: Forschungszentrum Jülich

Drugs can alter the structure of cell membranes.This can affect the effectiveness of the drugs or cause unwanted side effects. So far, however, these structural changes of cell membranes by medical drugs are little studied. Researchers from Jülich, Garching near Munich, Georgia and France want to change this. They have developed a new method for neutron research, which makes it easier and faster to detect membrane deformation than is possible with previous methods.

Cell membranes envelop the cells in the human body like a protective skin. They are very thin – 10,000 times thinner than a human hair. Its basis is a double layer of partly water-repellent molecules, so-called lipids. It contains a variety of protein molecules, which form, for example, ports for the import of nutrients and messengers into the cell interior or for the release of degradation products. These doors are often the drug’s point of attack.

The scientists of the Forschungszentrum Jülich, the Heinz Maier-Leibnitz Center in Garching, the Tbilisi State University in Georgia and the Laboratoire Léon Brillouin in Saclay, France, used a model system for their investigations that does not contain any stored proteins but the membrane of cells otherwise very similar is a double layer of soy lipids. An important advantage of this method is that structural changes in the very regular film can be more easily recognized. In addition, the researchers were able to apply these lipid layers to a flat surface for measurement. This also improves the measurement result.

To test their method, the researchers examined how two common medicinal drugs affect the structure of the membrane. They were able to prove that the local anesthetic benzocaine and the beta-blocker propranolol either stiffen the model membranes and make them brittle or grow connections between the two layers of the membrane. “Both are physiologically undesirable and could be the cause of side effects in overdose or long-term use of the drugs,” suspects. Henrich Frielinghaus.He is responsible for the Small Angle Scattering Diffractometer KWS-1, which is operated by the Jülich Center for Neutron Science (JCNS) at the Heinz Maier-Leibnitz Center in Garching. Such hypotheses can not be directly demonstrated by the new method. “The basic effect of the substances on membranes can be recognized very well. Our neutron examinations can thus provide information on whether further tests are meaningful, “says Frielinghaus. The researchers could test about ten active substances per day.

Source : Forschungszentrum Jülich