Lipid Areas Obtained from the Simultaneous Analysis of Neutron and X-ray Scattering

Abstract

Despite their importance to biophysical research, published lipid areas have been relatively scarce and for the most part, inconsistent. Noteworthy are the discrepancies between lipid areas as determined by standalone X-ray and neutron scattering experiments - arguably two of the most commonly used techniques in structural biology. Although they each have their advantages and disadvantages, when used in combination their advantages can be maximized. In particular, the large scattering contrast in the case of neutrons best resolves the overall bilayers thickness that is directly related to lipid lateral area. On the other hand, high resolution X-ray experiments yield detailed intra molecular structural information [Kucerka et al., Biophys. J. 95, 2356 (2008)].We have utilized our recently developed method to characterize lipid areas of various phospholipids with varying numbers of carbons and double bonds. In the case of lipids with unsaturated fatty acid chains our results suggest that lipid areas change with increasing hydrocarbon chain length, but not linearly - lateral lipid area is the result of the fine balance between the hydrocarbon chain length and double bond position. Furthermore, we discovered that the most dramatic change in lipid area occurs after the introduction of the first double bond to the lipid's acyl chains.Besides their importance in biology, lipid areas play a central role in molecular dynamics (MD) simulations, where their inconsistencies have been highlighted by the disparate results arising from MD simulations using different force fields. Since MD force fields are considered to be “well tuned” if they are able to reproduce experimental data, more reliable experimental information is necessary for their future development.