Neutron scattering techniques can resolve the complex three-dimensional atomic arrangements and real-time dynamics of biological membranes, which are important to understand cell function and drug delivery. The contrast, or difference in neutron scattering strength between individual components in a structure, is used to study specific molecules.

Researchers can vary this contrast to better see a structure’s shape and the interactions of its different components. Lakey et al. presented examples of neutron contrast variation to highlight how this tool can be exploited to visualize biological samples.

“By collecting these contrast-specific stories, we hope to make it easier for readers to learn more about the possibilities of contrast manipulation in biomolecular studies,” said author Jeremy Lakey.

The studies described used a range of contrast variation methods with two different neutron scattering techniques—small angle neutron scattering and neutron reflectometry—to study the bacterial outer membrane, which can impede antibiotics. The authors discussed the advantages and weaknesses of the different contrast variation approaches.

“There is still a need to find better ways to increase the variety and intensity of neutron contrasts in studies of complex biological systems,” Lakey said. “We hope this review will encourage others to experiment with new approaches to expand the current capabilities.”

The contrast variation approaches discussed in this review replaced hydrogen with deuterium, which could be improved with more selective deuteration. Additionally, alternative methods might substitute other elements, or achieve contrast variation through magnetic field effects, to learn more about cell membranes and other samples.

Source: “Exploiting neutron scattering contrast variation in biological membrane studies,” by Jeremy H. Lakey, Nicolò Paracini, and Luke A. Clifton, Biophysics Reviews (2022). The article can be accessed at