Neutrons produce the first direct 3D maps of water when melting cell membranes

New 3D maps of water distribution during cell membrane fusion accelerate the scientific understanding of cellular development, which could lead to new treatments for diseases associated with cell fusion. Using neutron diffraction at the Oak Ridge National Laboratory of the Department of Energy, researchers performed the first direct observations of water in lipid bilayers used to model cell membrane fusion.

The research, published in Journal of Physical Chemistry Letters, could provide new insights into diseases in which normal cell fusion is disrupted, such as Albers-Schönberg disease (osteopetrosis), help facilitate the development of fusion-based cell therapies for degenerative diseases and lead treatments that prevent fusion cells between cancer cells and non-cancer cells.

When two cells combine during fertilization or as membrane-bound vesicles fuse during the entry of the virus, neuronal signaling, placental development and many other physiological functions, semi-permeable membrane bilayers between partners of merger must be merged. As the two membranes get closer, the hydration forces increase exponentially, which requires a significant amount of energy for the membranes to overcome. The mapping of the distribution of water molecules is essential to understand the melting process.

The researchers used the small-angle neutron scattering instrument (EQ-SANS) at the ORNL spallation neutron source and the small-angle biological neutron scattering instrument (Bio- NO) to the high flux isotope reactor. size of a few nanometers.

"We used neutrons to probe our samples because water can not usually be seen by X-rays and because other imaging techniques can not accurately capture the extremely process. fast and dynamic cell fusion, "said Durgesh K. Rai. -author and now post-doctoral fellow at the Cornell High Energy Synchrotron Source of Cornell University. "In addition, the cold, low-energy neutrons of EQ-SANS and Bio-SANS will not cause radiation damage and will not introduce radicals that can interfere with lipid chemistry, as do X-rays".

The water density map of the researchers indicates that the water dissociates from the lipid surfaces in the initial lamellar phase or in layers. In the intermediate fusion phase, known as hemifusion, the water is drastically reduced and squeezed into pockets around a stem – a strongly curved lipidic "bridge" connecting two membranes before the merger does not occur completely.

"For the neutron scattering experiments, we replaced some hydrogen atoms with deuterium atoms, which helped the neutrons to observe the water molecules during the membrane fusion," said Shuo Qian, author of 'study. "The information we obtained could help in future studies of membrane-acting drugs, membrane-associated proteins and peptides in a membrane complex."

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The research was supported by DOE's Office of Science and ORNL Laboratory's research and development program.

The spallation neutron source and the high flux isotope reactor are user facilities of the DOE Science Office. UT-Battelle manages ORNL for the DOE Science Office. The Office of Science is one of the largest proponents of basic research in the physical sciences in the United States and is addressing some of the most pressing challenges of our time. For more information, go to http: // science.energy.gov /.