New method to obtain structure of biomembranes using diffuse x-ray scattering: Application to fluid phase DOPC lipid bilayers

This work focuses on the biologically relevant fluid phase of fully hydrated lipid bilayers. The goal to obtain the structure and the material parameters KC and B more accurately was achieved by studying diffuse x-ray scattering from stacks of oriented lipid bilayers. More information about bilayer structure and fluctuations was extracted from the diffuse scattering than can be obtained using conventional diffraction methods.; Sample preparation, chamber design, x-ray optical setup at CHESS synchrotron, data collection and image processing are explained. Scattering theory of smectic liquid crystal is derived in such a way that efficient computation is carried out. Experimental considerations on finite-size domains, x-ray coherence length, mosaic spread, CCD integration, and geometric broadening are incorporated into the model calculation with appropriate simplifications for efficiency. Nonlinear model fitting program was developed to obtain the material parameters and the form factors (up to qz = 0.79A -1) of the lipid samples. Discussions on area of fitting, input parameters and error estimation are presented. Improved hybrid Gaussian models were developed to construct the electron density profile of lipid bilayers by fitting the corresponding form factor. The improved models can incorporate volumetric information and/or simulation results in the form of hard or soft constraints. These constraints reduce over-fitting and lead to consistent electron density profile. An application of the methodology on the data sets of DOPC lipid bilayers at two hydration level demonstrates the great potential of this new method.