Nanoscale Structure of Lipid Bilayers Revealed By In-Silico and Experimental Small Angle Neutron Scattering

Abstract

Through the combination of simulations and numerical analysis with small angle neutron scattering, we probe the lateral organization of lipid bilayer mixtures. Small Angle Neutron Scattering (SANS) is an excellent complement to optical techniques, as it reveals molecular scale structural details without fluorescent probes. On its own, however, SANS is not sufficient to determine the organization of the membrane. We therefore take a two-pronged approach, comparing molecular dynamics simulations of ternary mixtures to experimental data obtained for the same mixtures. In-silico neutron scattering experiments on simulated membranes are compared to the experimental data, simultaneously validating the simulation data and providing a molecular scale model of the experimental system. Our all-atom molecular dynamics simulations use pre-existing software packages (e.g., Gromacs) to produce atomic trajectories of ten microseconds in length. These trajectories are processed and analyzed using custom software to generate scattering intensities for comparison to experiment, assuming laterally averaged scattering within nanoscopic domains. Simulated scattering intensities are fit to experimental data to extract information about the lateral structure. In this way, the transverse variation in scattering length density across the bilayer — which, under fully deuterated solvent, is much more significant than lateral contributions — is used to infer lateral structure.