Abstract
Biological membranes are composed of a thermally disordered lipid matrix and therefore require non-crystallographic scattering approaches for structural characterization with x-rays or neutrons. Here we develop a continuous distribution (CD) model to refine neutron or x-ray reflectivity data from complex architectures of organic molecules. The new model is a flexible implementation of the composition-space refinement of interfacial structures to constrain the resulting scattering length density profiles. We show this model increases the precision with which molecular components may be localized within a sample, with a minimal use of free model parameters. We validate the new model by parameterizing all-atom molecular dynamics (MD) simulations of bilayers and by evaluating the neutron reflectivity of a phospholipid bilayer physisorbed to a solid support. The determination of the structural arrangement of a sparsely-tethered bilayer lipid membrane (stBLM) comprised of a multi-component phospholipid bilayer anchored to a gold substrate by a thiolated oligo(ethylene oxide) linker is also demonstrated. From the model we extract the bilayer composition and density of tether points, information which was previously inaccessible for stBLM systems. The new modeling strategy has been implemented into the ga_refl reflectivity data evaluation suite, available through the National Institute of Standards and Technology (NIST) Center for Neutron Research (NCNR).
Highlights
Lipid bilayers in biological membranes are thermally disordered leaflets of fluid aliphatic molecules, assembled by hydrophobic interactions that expose a chemically diverse interface to their aqueous environment
One of these populations might be associated with fairly extended lipid hydrocarbon chains; a second would be related to highly disordered chains on which the methyl groups have a measurable probability of locating as far as away from the bilayer center as the lipid head groups
We demonstrate that the newly developed continuous distribution (CD) modeling procedure leads to a significant gain in the precision of the model parameters determined from the NR measurements of isotopically varied samples that is due to the intrinsic use of chemical constraints in the model parameterization
Summary
Lipid bilayers in biological membranes are thermally disordered leaflets of fluid aliphatic molecules, assembled by hydrophobic interactions that expose a chemically diverse interface to their aqueous environment They form the plasma membranes facing the intercellular space and the internal membranes that confine cell organelles. In both cases, the bilayer acts as a tightly controlled permeation barrier that interacts with proteins in a multitude of ways and mediates responses of the cell to external and internal cues. While simple slab models (“box” models) are still widely used in the evaluation of reflectometry data of membrane structures, such models cannot describe partial overlap of molecular fragments along the membrane normal Such a coexistence of distinct molecular components within the same cross-sectional area of the bilayer occurs generally in membranes. A software implementation of the model has been integrated into the reflectometry data evaluation program ga_refl by the NIST Center for Neutron Research (NCNR).
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