Understanding the properties and behavior of cell membranes can help scientists design better methods for drug delivery. However, some aspects of membranes and the lipid molecules that form them are difficult to investigate due to how quickly these molecules move. Researchers at NIST’s Center for Neutron Research (NCNR) and the SPring-8 synchrotron facility in Japan have collaborated to leverage advanced spectroscopy techniques to uncover some of the mysteries behind how membranes move and why.
Neutron spin echo (NSE) spectroscopy conducted at NCNR’s Center for High Resolution Neutron Scattering was used to obtain much of the data. The NSE experiments were performed using a model membrane nearly identical to natural cell membranes, with hydrogen-deuterium exchange used to provide better contrast for neutron scattering. NIST researchers explored two main types of molecular motion related to membrane viscosity; the rapid movement of acyl tails within the core of the lipid bilayer, and the movement of the full lipid molecules moving around one another in the membrane. Measuring these movements and the friction they produce allowed the researchers to determine the membrane’s viscosity.
The NSE data was further complemented by X-ray spectroscopy data obtained using SPring-8’s synchrotron radiation source. The results revealed that the movement of the tails, while still incredibly fast, was an order of magnitude slower than predicted based on the movement of 3D liquid oil. The tails were found to quiver about once every 10 picoseconds, and the slower-than-expected speed suggests that being packed into 2D layers generated greater friction due to the contact between the tails. The full lipid molecules were found to move about 10 times slower than the acyl tails. The friction between the molecules combined with friction between the tails produced a viscosity measure that falls in the middle of the range of viscosity estimates from past research efforts. These results were published in Physical Review Letters.
“Measuring the viscosity helps us understand how quickly things move around in the membrane and how long it takes to open the cell,” said Elizabeth Kelley, a NIST researcher and one of the authors on the study. “These sorts of insights may help us design drugs that take advantage of them.”
The molecular-scale motion data generated from this research can be further studied through computer simulations to gain more insights for drug discovery. The role of membrane viscosity in controlling molecular transport and structural changes makes this measurement especially useful for exploring new delivery methods.
Video Credit: NIST