Simulation-derived neutron scattering for lipid membranes
Date
2020
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
The integration of molecular dynamics simulation and small-angle neutron scattering can yield new insights about molecular-scale structure within a system. Independently, scattering intensity data may be difficult to interpret, especially when multiple structures exist at similar lengthscales. For molecular dynamics, limited computational resources impose a tradeoff between parameterization accuracy, system dimensions, and simulation duration. The validation of simulations against experimental scattering intensities establishes the appropriateness of the tradeoffs, while simultaneously offering a visual and quantitative aid for interpreting the scattering intensity features. Existing tools computed the scattering intensity using only the transverse structure (i.e., normal to the bilayer surface) from the simulated membrane, but this is a poor approximation when the bilayer has significant lateral (in-plane) structure. ☐ Presented are two new computational techniques to compute the small-angle neutron scattering intensity from a lipid bilayer molecular dynamics simulation. The first method, termed the "Dirac Brush", computes the exact spectra including spurious artifacts from the simulation's periodic boundary conditions. The second method, termed "PFFT", applies a mean-field approximation beyond a tunable cutoff, avoiding the periodicity artifacts of the Dirac Brush. Both methods are validated using a set of coarse-grained molecular dynamics simulations to demonstrate sensitivity to contributions from lateral structure. ☐ An additional technique is then presented to incorporate effects of curvature into the scattering intensity model. Curvature effects from both vesicle size and from dynamic fluctuations are modeled by geometrically deforming the transverse scattering length densities from a molecular dynamics simulation, and then mapping the new density profile over an arbitrary surface to model a larger vesicle. This new strategy was again validated against coarse-grained molecular dynamics simulations of vesicles of two different sizes, and the overall quality of the curvature model was exceptional. ☐ Finally, the new techniques for modeling lateral contributions and curvature effects were combined to analyze the scattering intensity of vesicles with compositions exhibiting the liquid-ordered phase. Simulation had previously indicated that these compositions may exhibit nanoscale substructure consisting of hexagonally packed saturated lipid chains and cholesterol. PFFT was used to model the lateral scattering contributions, with the curvature effects included separately. The effect of vesicle size polydispersity was also included in the model, and the overall fit to experimental scattering intensity was compared with and without the lateral contributions from PFFT. The fit with lateral contributions was superior to the fit without lateral contributions, suggesting that the simulation accurately represents the lateral structure within the membranes, confirming the presence of the hexagonally-packed nanoscale substructure.
Description
Keywords
Dirac Brush, Spectra, PFFT, Molecular-scale structure