Model-based approaches for the determination of lipid bilayer structure from small-angle neutron and X-ray scattering data

Some of our recent work has resulted in the detailed structures of fully hydrated, fluid phase phosphatidylcholine (PC) and phosphatidylglycerol (PG) bilayers. These structures were obtained from the joint refinement of small-angle neutron and X-ray data using the scattering density profile (SDP) models developed by Kucerka et al. (Biophys J 95:2356-2367, 2008; J PhysChemB116:232-239, 2012). In this review, we first discuss models for the standalone analysis of neutron or X-ray scattering data from bilayers, and assess the strengths and weaknesses inherent to these models. In particular, it is recognized that standalone data do not contain enough information to fully resolve the structure of naturally disordered fluid bilayers, and therefore may not provide a robust determination of bilayer structure parameters, including the much-sought-after area per lipid. We then discuss the development of matter density-based models (including the SDP model) that allow for the joint refinement of different contrast neutron and X-ray data, as well as the implementation of local volume conservation within the unit cell (i.e., ideal packing). Such models provide natural definitions of bilayer thicknesses (most importantly the hydrophobic and Luzzati thicknesses) in terms of Gibbs dividing surfaces, and thus allow for the robust determination of lipid areas through equivalent slab relationships between bilayer thickness and lipid volume. In the final section of this review, we discuss some of the significant findings/features pertaining to structures of PC and PG bilayers as determined from SDP model analyses.